Methods

ABSTRACT

A method for selecting or designing a compound expected to modulate the activity of Leukotriene C4 synthase (LTC4S), the method comprising the step of using molecular modelling means to select or design a compound that is predicted to interact with the catalytic site or a substrate binding region of LTC4S, wherein a three-dimensional structure of at least a part of the catalytic site or a substrate binding region of LTC4S is compared with a three-dimensional structure of a compound, and a compound that is predicted to interact with the said catalytic site or substrate binding region is selected. The selected compound may be predicted to bind to at least a part of a region of the structure termed the “GSH substrate binding cavity” (formed by residues including residues Arg51, Arg30, Arg104, Gln53, Asn55, Glu58, Tyr59, Tyr93, Tyr97, Ile27, Pro37, Leu108 of full length human LTC4S, or equivalent residues); the “lipophilic substrate binding crevice” (formed by residues including Ala20, Leu24, Ile27, Tyr59, Trp116, Ala112, Leu115, Leu108, Tyr109, Leu62, Val119, Thr66, Vall6 and Leu17, or equivalent residues); or the “catalytic site” (formed by residues including Arg104 or Arg31, or equivalent residues).

The present invention relates to methods for screening for modulators of LTC₄ synthase. It relates to the definition of a three-dimensional structure of LTC₄ synthase and methods based thereon.

Leukotriene C₄ (LTC₄) synthase (LTC4S) is a pivotal enzyme in the biosynthesis of leukotrienes, a family of paracrine hormones implicated in the pathophysiology of inflammatory and allergic disorders, in particular bronchial asthma (Samuelsson, B. Science 220, 568-75 (1983); and Lewis, R. A., Austen, K. F. & Soberman, R. J. N Engl J Med 323, 645-55 (1990)). Leukotrienes are formed by immunocompetent cells including neutrophils, eosinophils, basophils, mast cells, and macrophages, in response to a variety of immunological as well as non-immunological stimuli. These lipid mediators are divided into two major classes exemplified by the chemotaxin LTB₄, and the spasmogenic cysteinyl-leukotrienes (LTC₄, LTD₄, and LTE₄). Leukotriene biosynthesis is initiated by the enzyme 5-lipoxygenase (5-LO) which converts arachidonic acid into the unstable epoxide LTA₄, a central intermediate in the leukotriene cascade. LTA₄ may in turn be hydrolyzed into LTB₄ by the enzyme LTA₄ hydrolase, or conjugated with GSH to form LTC₄, a reaction catalyzed by the specific LTC4S. During cellular activation, all key enzymes in leukotriene biosynthesis, except LTA₄ hydrolase, form a biosynthetic complex assembled at the nuclear membrane, suggesting that leukotrienes may have unknown intranuclear functions related to gene regulation or cell growth (Serhan, C. N., Haeggstrom, J. Z. & Leslie, C. C. Faseb J 10, 1147-58 (1996)).

Leukotriene C₄, the natural product of LTC4S, may be cleaved by γ-glutamyl transpeptidase and a dipeptidase to yield LTD₄ and LTE₄, respectively. Together, these three leukotrienes constitute what was previously known as slow-reacting substance of anaphylaxis (SRS-A), a potent smooth muscle contracting agent with profound effects at only nM concentrations in the human respiratory system, where it elicits bronchoconstriction, and the microcirculation with increased leakage and oedema formation (Samuelsson, B. Science 220, 568-75 (1983)). Hence, cysteinyl-leukotrienes (cys-LT) are regarded as key mediators of inflammation and allergy, and have been implicated in a number of diseases, including nephritis, dermatitis, hay-fever, and in particular asthma and pulmonary fibrosis (Lewis, R. A., Austen, K. F. & Soberman, R. J. N Engl J Med 323, 645-55 (1990); Beller, T. C. et al. Proc Natl Acad Sci USA 101, 3047-52 (2004)). Furthermore, the role of cys-LT in inflammation and asthma has been well corroborated by the therapeutic potential and clinical use of molecules, which inhibit cys-LT biosynthesis as well as antagonists of the receptors for cys-LT (Drazen, J. M., Israel, E. & O'Byrne, P. Treatment of asthma with drugs modifying the leukotriene pathway. N. Engl. J. Med. 340, 197-206 (1999)). Moreover, reduced inflammatory reactions are observed in several animal models of leukotriene deficiency (Chen, X. S., Sheller, J. R., Johnson, E. N. & Funk, C. D. Nature 372, 179-182 (1994); Griffiths, R. J., et al. Proc Natl Acad Sci USA 92, 517-21 (1995); and Griffiths, R. J., et al. J Exp Med 185, 1123-9 (1997)). In addition, LTC₄ modulates the immune response, e.g., by interference with specific subsets of lymphocytes, production of cytokines, as well as liberation of immunoglobulins from B-lymphocytes (Payan, D. G., Missirian-Bastian, A. & Goetzl, E. J. Proc Natl Acad Sci USA 81, 3501-5 (1984); Rola-Pleszczynski, M. & Lemaire, I. J Immunol 135, 3958-61 (1985); and Yamaoka, K. A., Claesson, H. E. & Rosen, A. J Immunol 143, 1996-2000 (1989)).

LTC4S is a notoriously unstable, 18 kDa integral membrane enzyme, which has been purified to apparent homogeneity from KG-1 and THP-1 cells (Penrose, J. F. et al. Proc. Natl. Acad. Sci. USA 89, 11603-11606 (1992); Nicholson, D. W. et al. Proc. Natl. Acad. Sci. USA 90, 2015-2019 (1993). The cloning and molecular characterization of the enzyme unexpectedly revealed that LTC4S and FLAP are homologous proteins (Lam, B. K., et al. Proc. Natl. Acad. Sci. USA 91, 7663-7667 (1994); Welsch, D. J. et al. Proc. Natl. Acad. Sci. USA 91, 9745-9749 (1994)). Further studies showed that LTC4S is also distantly related to microsomal glutathione-5-transferases (MGST), in particular MGST2 and MGST3, and several functional links to LT metabolism have been established. Thus, human MGST2 and MGST3 both possess LTC₄ synthase activity and recent studies have shown that the main, if not the only, LTC₄ producing enzyme in human umbilical vein endothelial cells is MGST2, indicating that this enzyme plays a role in transcellular biosynthesis of LTC₄ in the vascular wall (Jakobsson, P.-J., et al. Prot. Sci. 8, 689-692 (1998)). Another enzyme homologous to LTC4S is microsomal prostaglandin (PG) E synthase type 1 (mPGES-1), which catalyzes the conversion of prostaglandin endoperoxides into the substance PGE2, an important mediator of inflammation, fever and pain (Jakobsson, P. J. et al. Proc. Natl. Acad. Sci. USA 96, 7220-7225 (1999)). Together, LTC4S, FLAP, MGST1, MGST2, MGST3, and microsomal prostaglandin (PG) E2 synthase, belong to a widespread protein superfamily designated MAPEG (membrane-associated proteins in eicosanoid and glutathione metabolism) (Jakobsson, P.-J., et al. Prot. Sci. 8, 689-692 (1998)).

Thus far, no detailed structural information is available for LTC4S or any other member of the MAPEG family. Some crude structural information has been obtained by electron microscopy, a technique which is very different from X-ray crystallography and which does not generate structures at atomic resolution. Thus, Schmidt-Krey et al. (Structure 12, 2009-14 (2004)) have described generation of 2-dimensional crystals of LTC4S from which a projection map could be calculated revealing a picture of its quaternary structure (trimer) and basic interrelationships of the transmembrane helices. A low-resolution (3.2 Å) structure of the detoxifying liver enzyme MGST-1 has also been determined (Holm et al (2006) J Mol Biol 360, 934-945. However, despite the well-recognized need thereof, the three-dimensional structure of LTC4S has not yet been disclosed.

More specifically, the problems that need to be overcome in order to provide such a determination may in brief be explained as follows. There are two major difficulties in obtaining a three-dimensional structure of a protein molecule, as discussed further below. The first one is to grow crystals of good quality that are reproducible and diffract to atomic resolution (beyond 2.5 Å). This means a thorough and cumbersome investigation of parameters that influence the crystal growth such as pH, temperature, nature of buffers, nature of precipitant, just to mention a few. The addition of ligands such as substrate analogues or inhibitors or the addition of other molecules can be important for obtaining good crystals. There is only little understanding of the physical background of the crystallisation process which means that the search for suitable crystallisation conditions for a certain protein is unique, requires creativity and intuition, and is governed by trial and error procedures. The purity of the protein is also a crucial parameter in the crystallisation and a suitable degree of purity can be hard, or even impossible, to achieve. Before suitable crystals have been obtained there is no guarantee that it will ever be possible to do so.

It should further be emphasized that all these problems are extremely hard to manage for membrane proteins, particularly integral membrane proteins, that are difficult to obtain in large and sufficiently pure amounts. Also, membrane proteins are hydrophobic, tend to aggregate, and have to be kept in solution by various detergents that interfere with the crystallisation process.

The second major difficulty is associated with overcoming the phase-problem which is inherent to X-ray diffraction methods. To be able to overcome this problem it is necessary to substitute the protein with suitable heavy atom substance such as e.g. mercury, gold or platinum compounds. Crystals often cannot withstand the treatment with these compounds and the search for suitable substitutions is not straight forward and may become very extensive. Another option is to substitute all methionines by seleno-methionine (Se-Met) residues. This method requires production of recombinant protein in special strains of E. coli under non-standard conditions, followed by a new purification and recrystallisation of the Se-Met containing protein.

It is important to note that although Schmidt-Krey et al reported the generation of 2-dimensional crystals of LTC4 synthase (ie a single layer or small number (for example less than 10) layers of LTC4 synthase homotrimers), these crystals can not be used for X-ray crystallography and determination of the three dimensional structure of the enzyme. For X-ray crystallography using current techniques it is necessary to have a 3-dimensional crystal ie with more than one layer of LTC4 synthase trimers, as is well known to those skilled in the art.

Thus, as a reliable definition of the three-dimensional structure of LTC4S would enable e.g. a display in visual form on a computer screen of the shape of the molecule, then, could the above mentioned problems be solved, a whole range of possibilities would be opened, such as rational structure-based drug design, e.g. in combination with combinatorial chemistry, aimed at production of novel medicaments useful in disorders associated with the leukotriene cascade, as well as protein-engineering to create novel variants of the enzyme with altered, but yet useful, properties.

As LTC4S is a recognized important drug target, some inhibitors thereof have been synthesized (Hutchinson, J. H. et al J. Med. Chem. 38, 4538-4547 (1995); Gupta, N., Nicholson, D. W., Ford-Hutchinson, A. W. Can. J. Physiol. Pharmacol. 75, 1212-1219 (1997)). Due to the absence of any available information regarding the three-dimensional structure of LTC4S, as discussed above, none of the previously described inhibitors have been designed based on the exact structure thereof. Accordingly, there is a need within this field of determining the three-dimensional structure of LTC4S in order to design more potent and selective inhibitors of LTC4S as well as modified structures exhibiting even more advantageous pharmaceutical properties.

The listing or discussion of a prior-published document in this specification should not necessarily be taken as an acknowledgement that the document is part of the state of the art or is common general knowledge.

We have crystallized and determined the three-dimensional structure of LTC4S complexed with the substrate glutathione. It is the first high-resolution three-dimensional structure of a member of the MAPEG family of proteins and enables a description of the structural basis and molecular mechanisms of catalysis. In addition, the structural information makes possible rational design of enzyme inhibitors, which may be developed into clinically useful anti-inflammatory drugs.

A first aspect of the invention provides a method for selecting or designing a compound expected to modulate the activity of Leukotriene C4 synthase (LTC4S), the method comprising the step of using molecular modelling means to select or design a compound that is predicted to interact with the catalytic site or a substrate binding region (together the active site) of LTC4S, wherein a three-dimensional structure of at least a part of the catalytic site or a substrate binding region of LTC4S is compared with a three-dimensional structure of a compound, and a compound that is predicted to interact with the said catalytic site or substrate binding region is selected.

The invention provides a computer-based method of rational drug design which comprises:

providing the structure of at least a part of the catalytic site or a substrate binding region of LTC4S (the protein) as defined by the coordinates of Table I or Table II ± the root mean square deviation from the backbone atoms of the protein of less than 2.0 Å, preferably less than 1.5 Å, 1.0 Å, or 0.5 Å; providing the structure of a candidate modulator molecule; and fitting the structure of the candidate modulator molecule to the structure of the protein.

By the term LTC4S is included the polypeptide termed LTC4S in Lam et al (1994) Expression cloning of a cDNA for human leukotriene C₄ synthase, an integral membrane protein conjugating reduced glutathione to leukotriene A₄ PNAS 91, 7663-7667 or Welsch et al (1994) Molecular cloning and expression of human leukotriene-C4 synthase PNAS 91, 9745-9749. LTC4S has EC number 4.4.1.20. The human LTC4S polypeptide sequence is presented below. The term “LTC4S” as used herein includes this polypeptide sequence as well as naturally occurring variants thereof. Further animal species also have equivalent polypeptides to LTC4S and are included within the scope of this term. Preferably, by LTC4S we mean the LTC4S polypeptide sequence shown below or a polypeptide sequence having at least 60, 65, 70, 75, 80, 85, 90, 95 or 98% identity thereto.

..1 Met Lys Asp Glu Val Ala Leu Leu Ala Ala .10 .11 Val Thr Leu Leu Gly Val Leu Leu Gln Ala .20 .21 Tyr Phe Ser Leu Gln Val Ile Ser Ala Arg .30 .31 Arg Ala Phe Arg Val Ser Pro Pro Leu Thr .40 .41 Thr Gly Pro Pro Glu Phe Glu Arg Val Tyr .50 .51 Arg Ala Gln Val Asn Cys Ser Glu Tyr Phe .60 .61 Pro Leu Phe Leu Ala Thr Leu Trp Val Ala . .70 .71 Gly Ile Phe Phe His Glu Gly Ala Ala Ala .80 .81 Leu Cys Gly Leu Val Tyr Leu Phe Ala Arg .90 .91 Leu Arg Tyr Phe Gln Gly Tyr Ala Arg Ser 100 101 Ala Gln Leu Arg Leu Ala Pro Leu Tyr Ala 110 111 Ser Ala Arg Ala Leu Trp Leu Leu Val Ala 120 121 Leu Ala Ala Leu Gly Leu Leu Ala His Phe 130 131 Leu Pro Ala Ala Leu Arg Ala Ala Leu Leu 140 141 Gly Arg Leu Arg Thr Leu Leu Pro Trp Ala 150

By the term LTC4S is included the polypeptide termed any mammalian or other LTC4S which has the same amino acid sequences as the human form with up to twenty, fifteen, ten, nine, eight, seven, six, five, four, three, two or one conservative or non-conservative substitutions therein. The amino acid sequences of mammalian LTC4S are about 90% identical. Thus, the three-dimensional structures are also expected to be identical to approximately the same extent. The term LTC4S does not encompass other members of the MAPEG family such as FLAP, MGST-1, MGST-2, MGST-3 or MPGES-1, as will be readily apparent to those skilled in the art.

In relation to polypeptides or structures used in screening methods or assays the term also includes fragments and fusions thereof that comprise the active site, as known to those skilled in the art. As LTC4S is a single-domain enzyme it is considered that fragments with extensive portions of the full length LTC4S sequence missing may not retain catalytic activity. However, fragments in which the C-terminal amino acids (for example C-terminal up to 20, 15, 10, 5, 4, 3, 2 or 1 amino acids) of full length LTC4S are missing are considered to retain catalytic activity. Since the active site of LTC4S is composed of amino acids from two adjacent monomers (Tables 1 and 2), a single polypeptide of LTC4S on its own is not sufficient for enzyme activity. Hence, in order to display catalytic activity, an LTC4S polypeptide must be complexed with another LTC4S polypeptide or a substitute polypeptide, for example a FLAP polypeptide, for example as described in Lam B K et al. (1997) J. Biol. Chem. 272(21):13923-8). Lam et al (1997) reports catalytic activity for a fusion of a LTC4S polypeptide and a FLAP polypeptide and for a fusion in which an internal segment of LTCS was replaced with a corresponding segment of FLAP. It is considered that wild-type LTC4S polypeptides spontaneously assemble into a catalytically active complex: it is preferred that the LTC4S fragment or fusion retains this ability.

The structure is typically (but not necessarily) a structure (or part of a structure) of an LTC4S polypeptide that retains LTC4S activity. For example, when in the form of a trimer or dimer, the LTC4S polypeptide is typically capable of conjugating glutathione with leukotriene A₄. Alternatively or in addition the LTC4S polypeptide retains fatty acid hydroperoxidase activity.

The following is an example of an assay that can be used in assessing the ability of a compound to modulate, for example inhibit, the action of LTC4S. In the assay LTC₄ synthase catalyses the reaction where the substrate LTA₄ methyl ester is converted to LTC₄ methyl ester. Purified recombinant human LTC₄ synthase (for example expressed in yeast) is dissolved in 25 mM Tris-buffer pH 7.8 and stored at −20° C. The assay is performed in phosphate buffered saline (PBS) pH 7.4, supplemented with 5 mM glutathione (GSH). The reaction is terminated by addition of acetonitrile/MeOH/acetic acid (50/50/1). The assay is performed at rt in 96-well plates. Analysis of the formed LTC₄ methyl ester is performed with reversed phase HPLC (Waters 2795 utilizing an Onyx Monolithic C18 column). The mobile phase consists of acetonitrile/MeOH/H₂O (32.5/30/37.5) with 1% acetic acid pH adjusted with NH₃ to pH 5.6, and absorbance measured at 280 nm with a Waters 2487 UV-detector.

The following is added sequentially to each well:

-   -   1. 50 μl assay buffer, PBS with 5 mM GSH.     -   2. 0.5 μl test compound in DMSO.     -   3. 2 μl LTC₄ synthase in PBS. The total protein concentration in         this solution is 0.025 mg/ml. Incubation of the plate at room         temperature for 10 minutes.     -   4. 0.5 μl LTA₄ methyl ester. Incubation of the plate at rt for 1         min.     -   5. 50 μl stop solution.         80 μl of the incubation mixture is analysed with HPLC.

Alternatively, an assay of the fatty acid hydroperoxidase activity can be used. For example: incubate 0.1-0.2 μg LTC4S in 50 μl 0.1 M K-phosphate pH 7.5 containing 1.5 mM GSH with 250 pmol hydroperoxide (13-HPOD, or 5-HPETE) at RT for 10 min. Terminate the reaction by the addition of 150 μl stop solution (MeCN:H2O:HOAc, 50:25:0.2, v/v). Analyse the conversion of the hydroperoxide into the corresponding alcohol by RP-HPLC, as described above, using a mobile phase composed of MeCN:H2O:HOAc, 60:40:0.1, v/v and the UV detector set at 235 nm.

Variations on these assays or alternative assays may be used, as will be well known to the skilled person.

We have found that LTC4S with an N-terminal hexahistidine tag is particularly beneficial for determining a structure for LTC4S. This fusion polypeptide has, for example, LTC4S activity and beneficial solubility and stability characteristics which make it particularly suitable for structural studies, for example formation of crystals which may be analysed by X-ray crystallography methods. It is considered that a fusion polypeptide with a different type of tag or different length histidine tag (for example a pentahistidine tag or septahistidine tag) may still be useful but is unlikely to be as useful as the fusion polypeptide with a hexahistidine tag. The size and metal ion co-ordination properties of the hexahistidine tag are considered to be particularly beneficial in forming well-diffracting crystals of LTC4S. The hexahistidine tag is considered to co-ordinate divalent metal ions, for example Nickel or Cobalt ions. It is considered that the crystals comprise neighbouring hexahistidine tags from more than one LTC4S trimer coordinated with metal ions. Accordingly, the structure can be one determined for LTC4S having an N-terminal hexahistidine tag.

It is particularly preferred that the structure is one determinable by a method as described in Example 1, for example a structure obtainable by X-ray analysis from a crystal obtainable using a mother liquor solution comprising a detergent. An example of a suitable detergent is dodecyl maltoside (DDM). Examples of other suitable detergents include the following:

-   CYMAL®-4 -   4-Cyclohexyl-1-butyl-β-D-maltoside¹ -   CAS #: 181135-57-9 -   .CYMAL®-5 -   5-Cyclohexyl-1-pentyl-β-D-maltoside¹ -   Formula Weight: 494.5 C₂₃H₄₂O₁₁ -   n-NONYL-®-D-MALTOPYRANOSIDE, ANAGRADE® -   n-Nonyl-®-D-maltoside -   CAS #: 106402-05-5 -   n-DECYL-®-D-MALTOPYRANOSIDE, ANAGRADE® -   n-Decyl-β-D-maltoside -   (Low Alpha) -   CAS #: 82494-09-5 -   Formula Weight: 482.6 C₂₂H₄₂O₁₁ -   n-UNDECYL-®-D-MALTOPYRANOSIDE, ANAGRADE® -   n-Undecyl-β-D-maltoside (Low alpha) -   CAS #: 253678-67-0 -   n-OCTYL-®-D-GLUCOPYRANOSIDE, ANAGRADE® -   n-Octyl-®-D-glucoside -   CAS #: 29836-26-8 -   Formula Weight: 292.4 C₁₄H₂₈O₆

Further preferred details of the crystallisation and X-ray analysis are described in Example 1.

It is particularly preferred that the structure is that represented by the structure co-ordinates shown in Table I (structure determined in the absence of glutathione; GSH) or II (structure determined in the presence of GSH), or a structure based or modelled on such a structure or co-ordinates, for example in which the root mean square deviation from the backbone atoms of the protein is less than 2.0 Å, preferably less than 1.5 Å, 1.0, or 0.5 Å.

The present application provides a listing illustrating the coordinates defining human LTC4S complexed to one of its substrates, glutathione, as well as a detergent molecule defining the binding site for the lipid substrate leukotriene A₄ (LTA₄). Based on their role in catalysis, the two binding sites occupied by glutathione and detergent define the active site of LTC4S and can be used as templates for design of molecules having desired properties. Methods for such design will be discussed in further detail below. The structural coordinates according to the invention are included in the present description as a separate section denoted “X-ray data”, as Tables I to II, immediately preceding the claims. These are co-ordinates for an LTC4S monomer and coordinated molecules. In Table I, atom no 1 to atom no 1263 define the LTC4S part of the complex. In table II, atom no 1 to atom no 1195 relate to the LTC4S whilst atom no 1233 to 1252 relate to glutathione. The atom numbers relating to the LTC4S are different in the two Tables because there are more residues visible in the first Table; tails aren't always visible in X-ray structures. Each active site within the homotrimer (or dimer) is formed by residues from two adjacent subunits within the homotrimer. The conditions prevailing at the determination thereof are described in detail in the Experimental section below.

As the skilled person in this field realises, such coordinates usually exhibit a certain degree of variation, due to e.g. thermal motion and slight differences in crystal packing. Thus, any references herein to Tables I to II in connection with the proteins and other molecules are merely intended to illustrate the coordinates defining the conformation of the molecules under identical conditions, as determined by use of the same apparatus and method.

The structure may be one determined following crystallisation in the presence of a known or potential interactor with LTC4S or modulator of LTC4S activity (as discussed further below), for example a known or potential inhibitor of LTC4S activity. The structure may, for example, be one determinable in the absence of glutathione (GSH) or in the presence of GSH. Examples of both are provided in Example 1. We have found that LTC4S crystallises in the presence of GSH. Alternatively, GSH can be absent during the initial crystallisation and then soaked into the crystal after it has formed.

For example, the structure may be one determined following crystallisation in the presence of a known LTC4S inhibitor, for example an inhibitor that is believed to bind to the GSH binding site; or an inhibitor that is believed to bind at the LTA4 binding site, such as cysteinyl-leukotrienes, LTC₄, LTD₄, or LTE₄, the 5-lipoxygenase inhibitors thiopyranol[2,3,4-c,d]indoles and L-699.333, the FLAP inhibitor MK886, or the CysLT receptor antagonist Montelukast. Co-crystals may form for inhibitors which are able respectively to displace GSH positioned in the GSH substrate binding cavity; or detergent positioned in the lipophilic substrate binding crevice; or at the catalytic part of the active site, as discussed in Example 1. The lipid substrate and GSH have different affinities for the active site. Thus, co-crystals may form with compounds targeted to the lipid binding site which have an IC50 of less than 100 μM, for example less than 10 μM or less than 1 μM (measured, for example, using LTA₄/GSH as the substrates), whereas compounds targeted to the GSH binding site may have an IC50 of less than 10 mM, for example less than 1 mM or less than 100 μM (measured, for example, using LTA₄/GSH as the substrate). It will be appreciated that some variation in crystallisation conditions (for example different mother liquors) may be required for co-crystallisation with different molecules. Techniques for investigating suitable crystallisation conditions in each case, starting from the information provided herein, will be well known to those skilled in the art. In one embodiment, co-crystallisation may be performed by diffusion of the co-crystallised molecule into a crystal of the polypeptide, for example a crystal obtained as set out in Example 1. This may be referred to as a “Soaking” procedure. If there is GSH or detergent positioned in the active site, as discussed in Example 1, co-crystallisation by diffusion/soaking may be easier to achieve, for example may require a lower concentration of the inhibitor, with an inhibitor with an IC50 of less than 10 μM, for example less than 1 μM or less than 100 nM.

It is considered that co-crystallisation may also be possible and useful with molecules with lower affinity for LTC4S, for example with IC50s in the millimolar range. For example, co-crystallisation may be useful with small molecules (“fragments”) considered to interact with part only of the active site. These small molecules may be useful as modules in designing/building a larger molecule with a lower IC50 for LTC4S inhibitor activity.

A further aspect of the invention provides a three-dimensional crystalline form of an LTC4S polypeptide (ie with multiple layers, for example more than 10 layers, preferably more than 100 layers of LTC4S homotrimers) as defined in relation to any one of the preceding aspects of the invention, for example a polypeptide consisting of full length human LTC4S with an N-terminal hexahistidine tag. The three dimensional crystalline form may belong to space group F23. A unit cell may contain 48 LTC4S chains and/or comprise multiple adjacent histidine tags coordinated by metal ions, as discussed further in Example 1 (for example three for each LTC4S trimer or twelve for each unit cell). The term “three-dimensional crystalline form” will be well known to those skilled in the art and does not encompass a two-dimensional (ie single or up to about 10 layer of LTC4S homotrimers) crystal form such as that described in Schmidt-Krey et al (1994) supra.

The crystalline form may further comprise a co-crystallised molecule, for example GSH or a detergent or other known or potential interactor with LTC4S or modulator of LTC4S activity, or a test compound (for example a small molecule considered to interact with only a part of the active site) whose properties vis a vis LTC4S may not be known. For example, the co-crystallised molecule, for example test compound, may be a molecule that is known to modulate LTC4S or other MAPEG family member activity; or may be an LTC₄ mimic or an LTA₄ mimic, or LTC₄ receptor agonist or antagonist; or a fatty acid hydroperoxide or mimic thereof, or another aliphatic compound (Thorén S and Jakobsson P J, Eur. J. Biochem. (2000) 267(21):6428-34; Schroder O et al., Biochem. Biophys. Res Commun. (2003), 312(2):271-6). Known LTC4 receptors include CysLT1, CysLT2 and GPR-17 (Ciana P et al. EMBO J. (2006), 25(19):4615-27). For example, the co-crystallised molecule may be a compound with an IC50 for LTC4S of less than 100 μM, typically less than 10 μM, 1 μM or 100 nM. The co-crystallised molecule may be a compound identified by a screening/design method of the invention, as discussed further below. The co-crystallised molecule may be a small compound thought to interact with only a part of the active site and having an IC50 in the millimolar range.

A further aspect of the invention accordingly provides a method for preparing a crystalline form of the invention, or for attempting to prepare a crystalline form of the invention, comprising 1) providing an LTC4S polypeptide as defined in relation to any of the preceding aspects of the invention; 2) providing a compound selected using a selection/design method of the invention (typically but not necessarily with a LTC4S IC50 of less than 100 μM, 10 μM, 1 μM or 100 nM; and 3) carrying out crystallisation trials on a composition comprising the polypeptide and the selected compound.

A further aspect of the invention provides the use of a polypeptide as defined in relation to any of the preceding aspects of the invention in generating a three-dimensional crystal or a structure of the active site or a substrate binding region (or at least a part any thereof) of LTC4S; or a three-dimensional crystal or a structure of the active site or a substrate binding region (or at least a part any thereof) of LTC4S bound to a test compound. Preferences for the test compound are as indicated above.

The crystalline form may be useful in generating X-ray diffraction data and a structure, as well known to those skilled in the art, for example using techniques similar to those described in Example 1. The structure determined for LTC4S, for example as described herein, may be used in structure solution and refinement, for example as described in Example 1.

Such co-crystallisation and structures determined from co-crystallised molecules may be useful in molecular modelling and in determining features of the polypeptide and compound that are important for interaction. This may be useful in designing or selecting further test compounds.

In one embodiment it is preferred that the modelled molecule is predicted to bind to a region of the structure termed the “GSH substrate binding cavity” (considered to be formed by residues including residues Arg51, Arg30, Arg104, Gln53, Asn55, Glu58, Tyr59, Tyr93, Tyr97, Ile27, Pro37, Leu108 of full length human LTC4S, or equivalent residues of other LTC4S polypeptide); the “lipophilic substrate binding crevice” (formed by residues including Ala20, Leu24, Ile27, Tyr59, Trp116, Ala112, Leu115, Leu108, Tyr109, Leu62, Val119, Thr66, Val16 and Leu17, or equivalent residues of other LTC4S polypeptide); or the “catalytic site” (residues including Arg104 or Arg31, or equivalent residues of other LTC4S polypeptide). Accordingly, the method may comprise comparing the structure of the compound with the structure of one or more of the regions mentioned above (or regions interacting with those regions).

TABLE 1 Residues lining the glutathione binding cavity Monomer1 Monomer2 Arg51 Ser23 Asn55 Val26 Glu58 Ile27 Tyr59 Arg30 Tyr93 Arg31 Tyr97 Pro37 Arg104 Tyr50 Leu108 Gln53

In Table 1, Arg51, Asn55, Glu58, Tyr59, Tyr93, Tyr97, Arg104, Arg30, and Gln 53 are highly conserved amino acids among members of the MAPEG family.

At this site, GSH is bound deep in a polar pocket at the interface between helix 1 and 2 from one monomer and 3 and 4 from a neighbouring monomer. The GSH molecule makes polar interactions to residues from both monomers constituting the active site. The carboxylate moieties of GSH make salt bridges to Arg51′ and Arg30 at the base of the binding pocket, effectively bending GSH and directing its thiol group towards the membrane interface where it interacts with Arg104′. Additional polar interactions to GSH are made by Gln53, Asn55′, Glu58′, Tyr59′, Tyr93′ and Tyr97′. Several non-polar interactions are also made (Ile27, Pro37 and Leu108′) providing an optimal fit for GSH into its binding pocket.

TABLE 2 Amino acids in the leukotriene binding site Monomer1 Monomer2 Tyr59 Val16 Leu62 Ala20 Ala101 Ser23 Gln102 Val26 Arg104 Ile27 Leu105 Ser28 Leu108 Arg30 Tyr109 Arg31 Ala112 Val35 Leu115 Ser36 Trp116 Pro37 Val119 Pro38

The present amino acids define the site binding the aliphatic side chain of the detergent DDM, a good mimic of LTA₄.

Here, Trp 116 forms the roof of the pocket, Tyr59, Ala20, and Leu62 form the floor and side walls, whereas Leu115 creates a bottom that restricts further intrusion of the ω-end of LTA₄ into the protein. At the opposite end of LTA₄, the carboxyl group is positioned in a wide section of the substrate binding cleft.

TABLE 3 Catalytic domain for LTC4S Monomer1 Monomer2 Arg51 Val16 Asn55 Ala20 Glu58 Ser23 Tyr59 Val26 Leu62 Ile27 Tyr93 Ser28 Tyr97 Arg30 Ala101 Arg31 Gln102 Val35 Arg104 Ser36 Leu105 Pro37 Leu108 Pro38 Tyr109 Tyr50 Ala112 Gln53 Leu115 Trp116 Val119

In Tables 1-3 above, the numbering of the amino acid sequence of LTC4S begin with the initial Met and is thus identical to the numbering in SEQ ID NO 1. The residues listed in Tables 1-3 are likely to define a common active site for homologues enzymes, i.e., other members of the MAPEG family.

It is preferred that the three-dimensional structure of at least a part of the active to site or a substrate binding region of LTC4S is a three-dimensional structure of at least a part of the “GSH substrate binding cavity”; the “lipophilic substrate binding crevice”; and/or the “catalytic site” or interacting regions, all as defined above, and a compound that is predicted to interact with the said “GSH substrate binding cavity”; “lipophilic substrate binding crevice”; and/or “catalytic site” or interacting regions of LTC4S is selected. Alternatively, the compound may bind to a portion of said LTC4S polypeptide that is not the “GSH substrate binding cavity”; “lipophilic substrate binding crevice”; and/or “catalytic site” or interacting regions of LTC4S, for example so as to interfere with the binding of a substrate molecule or its access to the catalytic site. In a still further example, the compound may bind to a portion of LTC4S so as to decrease said polypeptide's activity by an allosteric effect. This allosteric effect may be an allosteric effect that is involved in the natural regulation of LTC4S′ s activity.

The compound may bind to a portion of LTC4S that is involved in interaction between the subunits of the homotrimer. Residues considered to be involved in interaction between subunits are indicated in the following Tables. The subunits are indicated as subunits A, B and C, with the interactions of A with B and A with C indicated.

TABLE 4 Residue Number Residue Name Chain ID Protein Residue Contacts A B −4 HIS A −2 HIS A −1 HIS A 0 HIS A 1 HIS A 3 ASP A 4 GLU A 44 PRO A 47 GLU A 48 ARG A 51 ARG A 58 GLU A 59 TYR A 61 PRO A 62 LEU A 65 ALA A 66 THR A 69 VAL A 72 ILE A 73 PHE A 97 TYR A 101 ALA A 104 ARG A 108 LEU A 115 LEU A 116 TRP A 119 VAL A 122 ALA A 123 ALA A 126 LEU A 129 HIS A 130 PHE A Protein Residue Contacts B A −4 HIS B −3 HIS B −1 HIS B 0 HIS B 1 HIS B 2 LYS B 3 ASP B 5 VAL B 6 ALA B 7 LEU B 9 ALA B 10 ALA B 12 THR B 13 LEU B 16 VAL B 17 LEU B 19 GLN B 20 ALA B 23 SER B 24 LEU B 27 ILE B 30 ARG B 37 PRO B 38 PRO B 39 LEU B 40 THR B 50 TYR B 53 GLN B 54 VAL B 57 SER B 60 PHE B 61 PRO B 64 LEU B 68 TRP B Protein Residue Contacts A C −4 HIS A −3 HIS A −1 HIS A 0 HIS A 1 HIS A 2 LYS A 3 ASP A 5 VAL A 6 ALA A 7 LEU A 9 ALA A 10 ALA A 12 THR A 13 LEU A 16 VAL A 17 LEU A 19 GLN A 20 ALA A 23 SER A 24 LEU A 26 VAL A 27 ILE A 30 ARG A 37 PRO A 38 PRO A 39 LEU A 40 THR A 50 TYR A 53 GLN A 54 VAL A 57 SER A 60 PHE A 61 PRO A 64 LEU A 68 TRP A Protein Residue Contacts C A 1 GTT C −1 HIS C 0 HIS C 1 HIS C 3 ASP C 4 GLU C 44 PRO C 47 GLU C 48 ARG C 51 ARG C 58 GLU C 59 TYR C 61 PRO C 62 LEU C 65 ALA C 66 THR C 69 VAL C 72 ILE C 73 PHE C 97 TYR C 101 ALA C 104 ARG C 108 LEU C 115 LEU C 116 TRP C 119 VAL C 122 ALA C 123 ALA C 126 LEU C 129 HIS C 130 PHE C

Thus, a further aspect of the invention provides a method for selecting or designing a compound expected to modulate the activity of Leukotriene C4 synthase (LTC4S), the method comprising the step of using molecular modelling means to select or design a compound that is predicted to interact with a subunit interaction region of LTC4S, wherein a three-dimensional structure of at least a part of a subunit interaction region of LTC4S is compared with a three-dimensional structure of a compound, and a compound that is predicted to interact with the said substrate interaction region is selected. Residues involved in subunit interaction regions are indicated in the preceding Table 4.

It will be appreciated that a compound may have component parts that are predicted to interact with more than one part of LTC4S, for example more than one part of the LTC4S active site. For example, a compound may have a component part that interacts with the GSH substrate binding cavity of the LTC4S, as discussed above; and another component part that interacts with a different part of the LTC4S, for example with the “lipophilic substrate binding crevice”; and/or the “catalytic site” ie with other parts of the active site. A compound for further testing may be “assembled” from component parts (which may individually be very small) that are predicted to bind to different parts of the LTC4S, for example different parts of the LTC4S active site.

The three-dimensional structures may be displayed by a computer in a two-dimensional form, for example on a computer screen. The comparison may be performed using such two-dimensional displays.

The following relate to molecular modelling techniques: Blundell et at (1996) Structure-based drug design Nature 384, 23-26; Bohm (1996) Computational tools for structure-based ligand design Prog Biophys Mol Biol 66(3), 197-210; Cohen et al (1990) J Med Chem 33, 883-894; Navia et al (1992) Curr Opin Struct Biol 2, 202-210.

The following computer programs [wes1], for example, may be useful in carrying out the method of this aspect of the invention: GRID (Goodford (1985) J Med Chem 28, 849-857; available from Molecular Discovery, Pinner, UK); MOE (Chemical Computing Group, Montreal, Quebec, Canada); AUTODOCK (Goodsell et al (1990) Proteins: Structure, Function and Genetics 8, 195-202; available from Scripps Research Institute, La Jolla, Calif., USA); DOCK (Kuntz et al (1982) J Mol Biol 161, 269-288; available from the University of California, San Francisco, Calif.); LUDI (Bohm (1992) J Comp Aid Molec Design 6, 61-78; available from Accelrys, San Diego, Calif., USA); Sybyl (Tripos Associates, St Louis, Mo., USA); Gaussian 03, for example revision D (Gaussian, Inc., Pittsburgh, Pa., USA); AMBER (University of California at San Francisco, San Francisco, Calif., USA); QUANTA (Accelrys, San Diego, Calif., USA); and Insight II (Accelrys, San Diego, Calif., USA). Programs may be run on, for example, a Silicon Graphics™, an IBM RISC/6000™, or a Red Hat Enterprise Linux workstation.

Several in silico methods could be employed, for example as described in to Example 2, or via a substructure search for new ligands using programmes such as [wes2] Unity (Tripos Associates, St Louis, Mo., USA) or ChemFinder (CambridgeSoft, Cambridge, Mass., USA). The basic structure of the natural ligand (LTA₄ or GSH) or part thereof capable of binding to LTC4S is taken (or predicted) and various structural features of it (for example the hydrophobic and charged entities) are submitted to a programme which will search a set of chemical company catalogues for chemicals containing this substructure. For example the structure of the ends of GSH may be useful in searching for compounds which may interact with the GSH binding pocket or catalytic site, whilst the structure of LTA₄, for example its length, may be useful in searching for compounds which interact with the lipophilic substrate binding crevice.

These compounds are then screened, either using a computer or by eye, for groups that could not interact with portions of the catalytic site, for example the GSH substrate binding cavity (or other portion, as discussed above) because, for example, they are too large or have steric or charge hindrance, and those are discarded. The remaining chemicals are submitted to a PRODRG server and topologies/co-ordinates for these chemicals are created. These chemicals are modelled into the structure, from which chemicals that are possibly able to bind to the GSH substrate binding cavity/lipophilic substrate binding crevice/catalytic site/interacting regions are selected. Further details of the PRODRG programme are available at http://davapc1.bioch.dundee.ac.uk/programs/prodrg/prodrg.html.

An alternative approach is to use PRODRG: a tool for generating GROMOS/MOL2/WHATIF topologies and hydrogen atom positions from small molecule PDB files. Starting from the natural ligand the skilled person can computationally vary all possible groups at each site on the ligand, with a variety of new groups while the protein co-ordinates and the ligand back-bone co-ordinates remain fixed. The results can then be screened for hindrance, repulsion and attraction.

A starting compound may initially be selected by screening for an effect on LTC4S enzyme activity (for example using LTA₄ as a substrate); then compared with the structure; used as the basis for designing further compounds which may then be tested by further modelling and/or synthesis and assessment, as discussed further below.

The selected compounds may then be ordered or synthesised and assessed, for one or more of ability to bind to and/or modulate LTC4S activity. The compounds may be crystallised with the LTC4S polypeptide and the structure of any complex determined.

The method of the invention may further comprise the steps of providing, synthesising, purifying and/or formulating a compound selected using computer modelling, as described above; and of assessing whether the compound modulates the activity of LTC4S. The compound may be formulated for pharmaceutical use, for example for use in in vivo trials in animals or humans.

Thus, the present invention provides methods of structure-based design of LTC4S inhibitors. Such methods are based, for example, on the use of the present coordinates, or preferably the coordinates defining a selected region, as templates in order to synthesize advantageous inhibitors with strong and specific binding properties. More specifically, such methods can first use a conventional organic synthesis, alone or combined with combinatorial chemistry, wherein the structure of the product of the synthesis is then further refined by cycles of crystallisation of enzyme and inhibitor, followed by another chemical synthesis, the product of which is again refined, etc.

A compound that modulates the activity of LTC4S may be selected. For example, a compound that increases the activity of LTC4S may be selected, or a compound that decreases the activity of LTC4S may be selected. Situations in which each type of compound may be useful (or for which such a compound is a starting point for further investigations or compound design) are indicated below.

The ability of the compound to modulate the activity of LTC4S towards LTA₄ (5S,5,6-oxido-7,9-trans-11,14-cis eicosatetraenoic acid) may be assessed. Such assessment may also be carried out in a microtitre plate format or other format suitable for high throughput screening. The assessment may be carried out using enzyme assay techniques well known to those skilled in the art and as described below. The LTC4S polypeptide used in such an assay may be a LTC4S polypeptide that retains LTC4S activity, as discussed above. For example, a polypeptide comprising full length human LTC4S or comprising a fragment of human LTC4S, for example a fragment lacking up to the C-terminal 20, 10, 5, 4, 3, 2 or 1 amino acids may be used, as will be apparent to those skilled in the art. Any such competent fragment has to be present together with a complementary fragment to form an active dimer or trimer since the active site is composed of residues from two adjacent subunits: it is considered that assembly into such a dimmer or trimer occurs spontaneously, but they may also be connected by a linker, using standard techniques in protein engineering.

An example of an assay that can be used in assessing the ability of a compound to modulate, for example inhibit, the action of LTC4S is described above.

Alternatively, the ability of the compound to modulate the fatty acid hydroperoxidase activity of LTC4S may be measured. An example of a suitable assay is described above.

Whilst it is anticipated that a compound binding to the active site of LTC4S will modulate the LTC4S activity of LTC4S (for example as assessed by action on LTA₄), it is possible that other activities or properties of LTC4S may be modulated, for example subunit interactions or interactions with other polypeptides (for example other MAPEG family members, for example FLAP), phosphorylation (Gupta N et al. FEBS Lett. (1999) 449(1):66-70), or effects of divalent cations (Nicholson D W et al. Eur. J. Biochem. (1992) 209(2):725-34), or intramolecular interactions or interactions with other LTC4S or FLAP monomers or dimmers (Mandal A K et al Proc. Natl. Acad. Sci. USA (2004) 101(17):6587-92).

As noted above, the selected or designed compound may be synthesised (if not already synthesised) or purified and tested for its effect on LTC4S (or a fragment, variant or fusion with LTC4S activity), for example its effect on the LTC4S activity. The compound may be tested in an in vitro screen for its effect on a LTC4S polypeptide or on a cell or tissue in which LTC4S is present. The cell or tissue may contain endogenous LTC4S and/or may contain exogenous LTC4S (including LTC4S expressed as a result of manipulation of endogenous nucleic acid encoding LTC4S). The compound may be tested in an ex vivo or in vivo screen, which may use a transgenic animal or tissue. The compound may also be tested, for comparison, in a cell, tissue or organism that does not contain LTC4S (or contains reduced amounts of LTC4S), for example due to a knock-out or knock-down of one or more copies of the LTC4S gene. Suitable tests will be apparent to those skilled in the art and examples include assessment of effects in an animal or ex vivo model of inflammation. Example of suitable models include Zymosan induced peritonitis and ovalbumin-sensitized mice as an allergic asthma model. The compound may be tested in a human ex vivo model of inflammation, for example on human peripheral blood or human umbilical cord blood, or on cells isolated from human peripheral blood or human umbilical cord blood, for example on leukocytes, for example neutrophils, eosinophils, or mast cells.

Compounds may also be subjected to other tests, for example toxicology or metabolism tests, as is well known to those skilled in the art.

A compound which binds to the lipophilic substrate binding crevice may be a compound which is also capable of binding to the receptor for the product of an LTC4S, i.e. an LTC₄ receptor, e.g. on a cell, such as a mast cell. Examples of LTC₄ receptors include CysLT1, CysLT2 and GPR-17. Thus, such a compound may be useful as an LTC₄ antagonist or agonist. Appropriate tests may also be conducted to determine whether this is the case.

It is preferred that the LTC4S is a polypeptide which consists of the amino acid sequence of the LTC4S sequence referred to above or naturally occurring allelic variants thereof. It is preferred that the naturally occurring allelic variants are mammalian, preferably human. The LTC4S may be a fusion polypeptide, for example with an N-terminal hexahistidine tag or FLAP, as discussed above.

It is particularly preferred, although not essential, that the variant or fragment or derivative or fusion of the LTC4S, or the fusion of the variant or fragment or derivative has at least 30% of the enzyme activity of full-length human LTC4S with respect to the glutathione conjugation of LTA₄. It is more preferred if the variant or fragment or derivative or fusion of the said LTC4S, or the fusion of the variant or fragment or derivative has at least 50%, preferably at least 70% and more preferably at least 90% of the enzyme activity of LTC4S with respect to the glutathione conjugation of LTA₄. However, it will be appreciated that variants or fusions or derivatives or fragments which are devoid of enzymatic activity may nevertheless be useful, for example by interacting with another polypeptide. Thus, variants or fusions or derivatives or fragments which are devoid of enzymatic activity may be useful in a binding assay, which may be used, for example, in a method of the invention in which modulation of an interaction of a mutated LTC4S of the invention and a compound is measured.

By “variants” of a polypeptide we include insertions, deletions and substitutions, either conservative or non-conservative. In particular we include variants of the polypeptide where such changes do not substantially alter the activity of the said polypeptide, for example the LTC4S activity of LTC4S, as described above.

By “conservative substitutions” is intended combinations such as Gly, Ala; Val, Ile, Leu; Asp, Glu; Asn, Gln; Ser, Thr; Lys, Arg; and Phe, Tyr.

The one and three-letter amino acid code of the IUPAC-IUB Biochemical Nomenclature Commission is used herein. In particular, Xaa represents any amino acid. It is preferred that Xaa represents a naturally occurring amino acid. It is preferred that the amino acids are L-amino acids.

It is particularly preferred if the LTC4S variant has an amino acid sequence which has at least 65% identity with the amino acid sequence of LTC4S referred to above (eg in Lam et al (1994) supra), more preferably at least 70%, 71%, 72%, 73% or 74%, still more preferably at least 75%, yet still more preferably at least 80%, in further preference at least 85%, in still further preference at least 90% and most preferably at least 95% or 97% identity with the amino acid sequence defined above.

The percent sequence identity between two polypeptides may be determined using suitable computer programs, for example the GAP program of the University of Wisconsin Genetic Computing Group and it will be appreciated that percent identity is calculated in relation to polypeptides whose sequence has been aligned optimally.

The alignment may alternatively be carried out using the Clustal W program (Thompson et al (1994) Nucl Acid Res 22, 4673-4680). The parameters used may be as follows:

Fast pairwise alignment parameters: K-tuple (word) size; 1, window size; 5, gap penalty; 3, number of top diagonals; 5. Scoring method: x percent. Multiple alignment parameters: gap open penalty; 10, gap extension penalty; 0.05. Scoring matrix: BLOSUM.

It is preferred that the LTC4S has identical or conserved residues that are equivalent to Arg104 or Arg31; and/or Arg51, Arg30, Arg104, Gln53, Asn55, Glu58, Tyr59, Tyr93, Tyr97, Ile27, Pro37, Leu108 (GSH substrate binding cavity residues); and optionally also Ala20, Leu24, Ile27, Tyr59, Trp116, Ala112, Leu115, Leu108, Tyr109, Leu62, Val119, Thr66, Val16 and Leu17 (lipophilic substrate binding crevice residues). Other residues for which it may be desirable for the residues to be identical or conserved include other residues listed in tables 1, 2, 3 or 4 above.

A further aspect of the invention provides a mutated LTC4S polypeptide, wherein one or more residues equivalent to Arg51, Arg30, Arg104, Gln53, Asn55, Glu58, Tyr59, Tyr93, Tyr97, Ile27, Pro37, Leu 108, Ala20, Leu24, Ile27, Tyr59, Trp 116, Ala112, Leu115, Leu108, Tyr109, Leu62, Val119, Thr66, Val16 and Leu17 or Arg31 of full length human LTC4S is mutated.

The present invention relates to a mutated form of LTC4S, which mutated form comprises one or more of the mutations defined in the following Tables 5-7, wherein amino acids are given in single letter code. Thus, R51G/AN/L/I/S/T/D/E/N/Q/H/K/P/C/M/F/Y/W indicates that residue arginine 51, using the LTC4S numbering scheme, is modified to an alanine, valine, a leucine and so forth.

TABLE 5 Mutations in the active site (GSH binding site) R30G/A/V/L/I/S/T/D/E/N/Q/H/K/P/C/M/F/Y/W 5(1) R51G/A/V/L/I/S/T/D/E/N/Q/H/K/P/C/M/F/Y/W 5(2) Q53G/A/V/L/I/S/T/D/E/N/R/H/K/P/C/M/F/Y/W 5(3) N55G/A/V/L/I/S/T/D/E/R/Q/H/K/P/C/M/F/Y/W 5(4) E58G/A/V/L/I/S/T/D/N/Q/R/H/K/P/C/M/F/Y/W 5(5) Y59G/A/V/L/I/S/T/D/E/N/Q/R/H/K/P/C/M/F/W 5(6) Y93G/A/V/L/I/S/T/D/E/N/Q/R/H/K/P/C/M/F/W 5(7) Y97G/A/V/L/I/S/T/D/E/N/Q/R/H/K/P/C/M/F/W 5(8) R104G/A/V/L/I/S/T/D/E/N/Q/H/K/P/C/M/F/Y/W 5(9)

TABLE 6 Mutations in the active site (LTA4 binding site) A20G/V/L/I/S/T/D/E/N/Q/R/H/K/P/C/M/F/Y/W 6(1) Y59G/A/V/L/I/S/T/D/E/N/Q/R/H/K/P/C/M/F/W 6(2) L62G/A/V/I/S/T/D/E/N/Q/R/H/K/P/C/M/F/Y/W 6(3) L115G/A/V/I/S/T/D/E/N/Q/R/H/K/P/C/M/F/Y/W 6(4) W116G/A/V/L/I/S/T/D/E/N/Q/R/H/K/P/C/M/F/Y 6(5)

More specifically, this embodiment relates to a mutant comprising any combination of at least two mutated amino acids, or any one of the above mentioned sequences of mutations, or any separate one amino acid mutation selected from the group consisting of sequences nos (5)1-9, 6(1-5).

The mutated LTC4S may be useful in determining where on the LTC4S a polypeptide or compound of interest interacts. For example, the abilities of a compound (including polypeptide) to bind to the mutated and unmutated LTC4S, or to modulate the activity of the LTC4S may be measured and compared.

A further aspect of the invention provides a polynucleotide encoding a mutated LTC4S polypeptide of the invention. A still further aspect of the invention provides a recombinant polynucleotide suitable for expressing a mutated LTC4S of the invention. A yet further aspect of the invention provides a host cell comprising a polynucleotide of the invention.

A further aspect of the invention provides a method of making a mutated LTC4S of the invention, the method comprising culturing a host cell of the invention which expresses said mutated LTC4S and isolating said mutated LTC4S.

A further aspect of the invention provides a mutated LTC4S obtainable by the above method.

Examples of these aspects of the invention may be prepared using routine methods by those skilled in the art.

For example, the above mutated LTC4S may be made by methods well known in the art, for example using molecular biology methods or automated chemical peptide synthesis methods.

It will be appreciated that peptidomimetic compounds may also be useful. Thus, by “polypeptide” or “peptide” we include not only molecules in which amino acid residues are joined by peptide (—CO—NH—) linkages but also molecules in which the peptide bond is reversed. Methods of designing and making peptidomimetic compounds will be known to those skilled in the art.

The invention further provides a method of identifying or characterising a compound that modulates the activity of LTC4S, comprising the step of determining the effect of the compound on the LTC4S activity of, or ability of the compound to bind to, the said mutated LTC4S of the invention.

The method may further comprise determining the effect of the compound on the LTC4S activity of, or ability of the compound to bind to, the LTC4S which is not mutated at the said residue.

For example, as will be apparent to the skilled person it may be helpful to compare the effect of a compound on wild-type (unmutated) LTC4S and a mutated LTC4S in which residue(s) (for example residue(s) which a test compound is expected, for example from computer modelling studies, to interact with) are mutated, in order to confirm or otherwise that the compound is binding as expected.

It will be appreciated that the LTC4S or mutated LTC4S may be a fusion protein comprising a tag, for example to aid purification or crystallisation, for example a hexahistidine tag, as described in Example 1.

A further aspect of the invention provides a kit of parts useful in carrying out a method according to the preceding aspect of the invention, comprising (1) a mutated LTC4S of the invention and (2) the corresponding LTC4S which is not so mutated.

The capability of the said LTC4S polypeptide with regard to interacting with or binding to a compound (which may be a polypeptide) may be measured by any method of detecting/measuring a protein/protein interaction or other compound/protein interaction, as discussed further below. Suitable methods include methods such as, for example, yeast two-hybrid interactions, co-purification, ELISA, co-immunoprecipitation and surface plasmon resonance methods. Thus, the LTC4S polypeptide may be considered capable of binding to or interacting with a polypeptide or other compound If an interaction may be detected between the LTC4S polypeptide and the compound or polypeptide by ELISA, co-immunoprecipitation or surface plasmon resonance methods or by a yeast two-hybrid interaction or copurification method. It is preferred that the interaction can be detected using a surface plasmon resonance method. Surface plasmon resonance methods are well known to those skilled in the art. Techniques are described in, for example, O'Shannessy D J Determination of kinetic rate and equilibrium binding constants for macromolecular interactions: a critique of the surface plasmon resonance literature. Curr Opin Biotechnol. 1994 February; 5(1):65-71; Fivash M, Towler E M, Fisher R J BIAcore for macromolecular interaction. Curr Opin Biotechnol. 1998 February; 9(1):97-101; Malmqvist M BIACORE: an affinity biosensor system for characterization of biomolecular interactions. Biochem Soc Trans. 1999 February; 27(2):335-40.

The effect of the compound on the LTC4S activity of LTC4S may be assessed, as indicated above. A compound may be selected that decreases the LTC4S activity of LTC4S. Such compounds may thus be useful in the treatment of those conditions in which it is required that the formation of e.g. LTC₄, LTD₄ or LTE₄ is inhibited or decreased, or where it is required that the activation of a Cys-LT receptor (e.g. Cys-LT₁ or Cys-LT₂) is inhibited or attenuated. The compounds of the invention may also inhibit microsomal glutathione S-transferases (MGSTs), such as MGST-I, MGST-II and/or MGST-III, thereby inhibiting or decreasing the formation of LTD₄, LTE₄ or, especially, LTC₄.

Such compounds are thus expected to be useful in the treatment of disorders that may benefit from inhibition of production (i.e. synthesis and/or biosynthesis) of leukotrienes (such as LTC₄), for example a respiratory disorder and/or inflammation. Further tests may be performed to assess the suitability of the compound for the treatment of such a disorder and/or inflammation, as will be well known to those skilled in the art.

The term “inflammation” will be understood by those skilled in the art to include any condition characterised by a localised or a systemic protective response, which may be elicited by physical trauma, infection, chronic diseases, such as those mentioned hereinbefore, and/or chemical and/or physiological reactions to external stimuli (e.g. as part of an allergic response). Any such response, which may serve to destroy, dilute or sequester both the injurious agent and the injured tissue, may be manifest by, for example, heat, swelling, pain, redness, dilation of blood vessels and/or increased blood flow, invasion of the affected area by white blood cells, loss of function and/or any other symptoms known to be associated with inflammatory conditions.

The term “inflammation” will thus also be understood to include any inflammatory disease, disorder or condition per se, any condition that has an inflammatory component associated with it, and/or any condition characterised by inflammation as a symptom, including inter alia acute, chronic, ulcerative, specific, allergic and necrotic inflammation, and other forms of inflammation known to those skilled in the art. The term thus also includes, for the purposes of this invention, inflammatory pain, pain generally and/or fever.

Accordingly, such compounds may be useful in the treatment of allergic disorders, asthma, childhood wheezing, chronic obstructive pulmonary disease, bronchopulmonary dysplasia, cystic fibrosis, interstitial lung disease (e.g. sarcoidosis, pulmonary fibrosis, scleroderma lung disease, and usual interstitial in pneumonia), ear nose and throat diseases (e.g. rhinitis, nasal polyposis, and otitis media), eye diseases (e.g. conjunctivitis and giant papillary conjunctivitis), skin diseases (e.g. psoriasis, dermatitis, and eczema), rheumatic diseases (e.g. rheumatoid arthritis, arthrosis, psoriasis arthritis, osteoarthritis, systemic lupus erythematosus, systemic sclerosis), vasculitis (e.g. Henoch-Schonlein purpura, Löffler's syndrome and Kawasaki disease), cardiovascular diseases (e.g. atherosclerosis), gastrointestinal diseases (e.g. eosinophilic diseases in the gastrointestinal system, inflammatory bowel disease, irritable bowel syndrome, colitis, celiaci and gastric haemorrhagia), urologic diseases (e.g. glomerulo-nephritis, interstitial cystitis, nephritis, nephropathy, nephrotic syndrome, hepatorenal syndrome, and nephrotoxicity), diseases of the central nervous system (e.g. cerebral ischemia, spinal cord injury, migraine, multiple sclerosis, and sleep-disordered breathing), endocrine diseases (e.g. autoimmune thyroiditis, diabetes-related inflammation), urticaria, anaphylaxis, angioedema, oedema in Kwashiorkor, dysmenorrhoea, burn-induced oxidative injury, multiple trauma, pain, toxic oil syndrome, endotoxin chock, sepsis, bacterial infections (e.g. from Helicobacter pylori, Pseudomonas aerugiosa or Shigella dysenteriae), fungal infections (e.g. vulvovaginal candidasis), viral infections (e.g. hepatitis, meningitis, parainfluenza and respiratory syncytial virus), sickle cell anemia, hypereosinofilic syndrome, and malignancies (e.g. Hodgkins lymphoma, leukemia (e.g. eosinophil leukemia and chronic myelogenous leukemia), mastocytos, polycytemi vera, and ovarian carcinoma). In particular, compounds of the invention may be useful in treating allergic disorders, asthma, rhinitis, conjunctivitis, COPD, cystic fibrosis, dermatitis, urticaria, eosinophilic gastrointestinal diseases, inflammatory bowel disease, rheumatoid arthritis, osteoarthritis and pain.

Such compounds may be useful for either the therapeutic and/or prophylactic treatment of the above-mentioned conditions.

A compound that increases the LTC₄ synthase activity of LTC4S may be useful in situations in which enhanced production of LTC₄, LTD₄ and/or LTE₄ is useful, for example in enhancing an immune response, for example in patients with an impaired immune response.

It will be appreciated that the invention provides screening assays for use in trying to identify drugs which may be useful in modulating, for example either enhancing or inhibiting, the LTC4S activity of LTC4S. Compounds identified in the methods may themselves be useful as a drug or they may represent lead compounds for the design and synthesis of more efficacious compounds.

The compound may be a drug-like compound or lead compound for the development of a drug-like compound for each of the above methods of identifying a compound. It will be appreciated that the said methods may be useful as screening assays in the development of pharmaceutical compounds or drugs, as well known to those skilled in the art.

The term “drug-like compound” is well known to those skilled in the art, and may include the meaning of a compound that has characteristics that may make it suitable for use in medicine, for example as the active ingredient in a medicament. Thus, for example, a drug-like compound may be a molecule that may be synthesised by the techniques of organic chemistry, less preferably by techniques of molecular biology or biochemistry, and is preferably a small molecule, which may be of less than 5000 daltons and more preferably less than 1000, 750 or 500 daltons. A drug-like compound may additionally exhibit features of selective interaction with a particular protein or proteins and be bioavailable and/or able to penetrate cellular membranes, but it will be appreciated that these features are not essential.

The term “lead compound” is similarly well known to those skilled in the art, and may include the meaning that the compound, whilst not itself suitable for use as a drug (for example because it is only weakly potent against its intended target, non-selective in its action, unstable, difficult to synthesise or has poor bioavailability) may provide a starting-point for the design of other compounds that may have more desirable characteristics.

It will be understood that it will be desirable to identify compounds that may modulate the activity of LTC4S in vivo. Thus it will be understood that reagents and conditions used in the method may be chosen such that the interactions between, for example, the LTC4S and the substrate, are similar to those between the human LTC4S and a naturally occurring substrate (for example LTA₄). As well known to those skilled in the art, different assay systems may be used to assess a compound, in some of which the convenience of the assay or the specificity for an effect on LTC4S may be optimised, whilst in others the in vivo relevance may be optimised, for example by assessing the effect of the compound in a whole cell.

The compounds that are tested in the screening methods of the assay or in other assays in which the ability of a compound to modulate the LTC4S activity of LTC4S may be measured, may be compounds that have been selected and/or designed (including modified) using molecular modelling techniques, for example using computer techniques.

The invention also provides a means for homology modelling of related proteins (referred to below as target proteins). By “homology modelling” is meant the prediction of related MAPEG family member structures based either on x-ray crystallographic data or computer-assisted de novo prediction of structure, based upon manipulation of the coordinate data of Tables I to II.

“Homology modelling” extends to target MAPEG proteins, which are related the human LTC4S protein whose structure has been determined in the accompanying examples. It also extends to LTC4S mutants.

In general, the method involves comparing the amino acid sequences of the LTC4S protein of Table I or II with a target MAPEG family member protein by aligning the amino acid sequences. Amino acids in the sequences are then compared and groups of amino acids that are homologous (referred to as “corresponding regions”) are grouped together. This method identifies conserved regions of the polypeptides and accounts for amino acid insertions or deletions. Alignment of MAPEG family sequences in view of the structural information obtained from LTC4S is discussed in Example 1 and an alignment is shown in FIG. 6.

Homology between amino acid sequences can alternatively or in addition be determined using commercially available algorithms, as discussed above. Once the amino acid sequences of the polypeptides with known and unknown structures are aligned, the structures of the conserved amino acids in a computer representation of the polypeptide with known structure are transferred to the corresponding amino acids of the target protein. For example, a tyrosine in the amino acid sequence of known structure may be replaced by a phenylalanine, the corresponding homologous amino acid in the amino acid sequence of the target protein.

The structures of amino acids located in non-conserved regions may be assigned manually by using standard peptide geometries or by molecular simulation techniques, such as molecular dynamics. The final step in the process can be accomplished by refining the entire structure using molecular dynamics and/or energy minimization.

Homology modelling as such is a technique that is well known to those skilled in the art (see e.g. Greer, Science, Vol. 228, (1985), 1055, and Blundell et al., Eur. J. Biochem, Vol. 172, (1988), 513). The techniques described in these references, as well as other homology modelling techniques generally available in the art, may be used in performing the present invention.

Thus, a further aspect of the invention provides a method of predicting a three dimensional structure of a target LTC4S protein or other MAPEG family member protein or homo- or heteromultimer thereof (the target protein), the method comprises the steps of: aligning a representation of an amino acid sequence of the target protein with the amino acid sequence of the LTC4S of Table I or II, optionally varied by a root mean square deviation of not more than 2.0 Å, preferably less than 1.5 Å, 1.0, 0.5 Å, or selected coordinates thereof, to match homologous regions of the amino acid sequences; modelling the structure of the matched homologous regions of said target protein on the corresponding regions of the LTC4S structure as defined by Table I or II, optionally varied by a root mean square deviation of not more than 2, 1.5 or 1 Å, or selected coordinates thereof; and determining a conformation for said target protein which substantially preserves the structure of said matched homologous regions.

Preferably the method is performed using computer modelling.

The MAPEG family member may be FLAP, MGST1, MGST2, MGST3, MPGES-1 or an LTC4S protein. Typically, the structure of the MAPEG family member may be unknown or known only at low resolution, for example at less than 2.5 Å resolution. The predicted structure may, for example, be a predicted structure for a heteromultimer (heterodimer) of a LTC4S polypeptide with a FLAP polypeptide, or a fusion in which an internal segment of LTCS is replaced with a corresponding segment of FLAP, as noted above.

A further aspect of the invention provides a method of obtaining a structure of a target LTC4S protein or other MAPEG family member protein or homo- or heteromultimer thereof (the target protein), the method comprises the steps of: providing a crystal of said target protein; obtaining an X-ray diffraction pattern of said crystal; calculating a three-dimensional atomic coordinate structure of said target protein, by modelling the structure of said target protein on the LTC4S structure of Table I or II ± the root mean square deviation from the backbone atoms of the protein of less than 2.0 Å, preferably less than 1.5 Å, 1.0, or 0.5 Å, or selected coordinates thereof.

Thus, the present LTC4S structure may be useful in interpreting X-ray diffraction data from a related polypeptide.

In a further aspect of the invention, the 3D structure of LTC4S, as provided herein, can be used to interpret electron crystallographic data to generate a structure from 2D crystals. Accordingly, a further aspect of the invention provides a method of obtaining a structure of a target LTC4S protein or other MAPEG family member protein or homo- or heteromultimer thereof (the target protein), the method comprises the steps of: providing a crystal of said target protein; obtaining an electron diffraction pattern of said crystal; calculating a three-dimensional atomic coordinate structure of said target protein, by modelling the structure of said target protein on the LTC4S structure of Table I or II ± the root mean square deviation from the backbone atoms of the protein of less than 2.0 Å, preferably less than 1.5 Å, 1.0, or 0.5 Å, or selected coordinates thereof. The crystal can be a 2D crystal.

A further aspect of the invention provides a method for selecting or designing a compound expected to modulate the activity of a MAPEG family member protein or homo- or heteromultimer thereof, the method comprising the step of using molecular modelling means to select or design a compound that is predicted to interact with the catalytic site or a substrate binding region of the MAPEG family member protein or homo- or heteromultimer thereof, wherein a three-dimensional structure of at least a part of the catalytic site or a substrate binding region of the MAPEG family member protein or homo- or heteromultimer thereof is compared with a three-dimensional structure of a compound, and a compound that is predicted to interact with the said catalytic site or substrate binding region is selected, wherein the three-dimensional structure of at least a part of the catalytic site or a substrate binding region of the MAPEG protein or complex thereof is a three-dimensional structure (or part thereof) predicted or obtained by a method according to the preceding three aspects of the invention.

In the methods of the invention for selecting or designing a compound, the molecular structure to be fitted may be in the form of a model of a pharmacophore.

A further aspect of the invention provides a computer-based method of rational drug design comprising: (a) providing the coordinates of a LTC4S structure as defined in Table I or II optionally varied by a root mean square deviation of backbone atoms of the protein of less than 2.0, 1.5, 1.0 or 0.5 Å, or selected coordinates thereof; (b) providing the structures of a plurality of molecular fragments; (c) fitting the structure of each of the molecular fragments to the selected coordinates; and (d) assembling the molecular fragments into a single molecule to form a candidate modulator molecule.

The method may further comprise the step of: (a) obtaining or synthesising the molecular fragment or modulator molecule; and (b) contacting the molecular fragment or modulator molecule with LTC4S to determine the ability of the molecular fragment or modulator molecule to interact with LTC4S.

The selected coordinates may be coordinates defining the active site, for example substrate binding regions or catalytic site, as discussed above. Fragments may, for example, be fitted to different parts of the active site and may then be assembled together, using techniques well known to those skilled in the art. See, for example, Hajduk & Greer (2007) Nature Reviews Drug Discovery 6, 211-219.

A further aspect of the invention provides a method of obtaining a representation of the three dimensional structure of LTC4S, which method comprises providing the data of Table I or II optionally varied by a root mean square deviation of backbone atoms of the protein of less than 2.0, 1.5, 1.0 or 0.5 Å, or selected coordinates thereof, and constructing a three-dimensional structure representing said coordinates.

The structure may be presented as, for example, (a) a wire-frame model; (b) a chicken-wire model; (c) a ball-and-stick model; (d) a space-filling model; (e) a stick-model; (f) a ribbon model; (g) a snake model; (h) an arrow and cylinder model; (i) an electron density map; (j) a molecular surface model.

A further aspect of the invention provides computer readable storage medium or a computer system, intended to generate structures and/or perform optimisation of compounds which interact with LTC4S or other MAPEG family member protein or homo- or heteromultimer thereof, complexes of LTC4S or other MAPEG family member protein or homo- or heteromultimer thereof with compounds, the storage medium or system containing computer-readable data comprising one or more of: (a) LTC4S co-ordinate data of Tables I or II optionally varied by a root mean square deviation of backbone atoms of the protein of less than 2.0, 1.5, 1.0 or 0.5 Å, or selected coordinates thereof, said data defining the three-dimensional structure of LTC4S or said selected coordinates thereof; (b) atomic coordinate data of a target MAPEG family member protein or homo- or heteromultimer thereof generated by homology modelling of the target based on the coordinate data of Table I or II optionally varied by a root mean square deviation of backbone atoms of the protein of less than 2.0, 1.5, 1.0 or 0.5 Å, or selected coordinates thereof; (c) atomic coordinate data of a target MAPEG family member protein or homo- or heteromultimer thereof generated by interpreting X-ray crystallographic data or NMR data by reference to the co-ordinate data of Tables I or II optionally varied by a root mean square deviation of backbone atoms of the protein of less than 2.0, 1.5, 1.0 or 0.5 Å, or selected coordinates thereof; (d) structure factor data derivable from the atomic coordinate data of (b) or (c); and (e) atomic coordinate data of Table I or II optionally varied by a root mean square deviation of backbone atoms of the protein of less than 2.0, 1.5, 1.0 or 0.5 Å, or selected coordinates thereof.

Such a computer system may be useful in performing a selection or design method of the invention.

The term “computer-readable storage medium” will be well known to those skilled in the art and includes any medium or media which can be read and accessed directly by a computer. Such media include, but are not limited to: magnetic storage media such as floppy discs, hard disc storage medium and magnetic tape; optical storage media such as optical discs or CD-ROM; electrical storage media such as RAM and ROM; and hybrids of these categories such as magnetic/optical storage media.

The term “a computer system” will also be well known to those skilled in the art and includes the hardware means, software means and data storage means used to analyse the atomic coordinate data of the present invention. The minimum hardware means of the computer-based systems of the present invention typically comprises a central processing unit (CPU), a working memory and data storage means, and e.g. input means, output means etc. A monitor may also be provided to visualize structure data. The data storage means may be RAM or means for accessing computer readable media of the invention. Examples of such systems are microcomputer workstations available from Silicon Graphics Incorporated and Sun Microsystems running Unix based, Linux based, Windows NT or IBM OS/2 operating systems. It will be appreciated that the methods of the invention may be performed by remote access to the atomic coordinate data of the present invention, for example using the internet.

All documents referred to herein are hereby incorporated by reference.

The invention is now described in more detail by reference to the following, non-limiting, Figures and Examples. All the references given below, and previously in this specification, are hereby included herein by reference.

FIG. 1 Key Enzymes and Intermediates in Leukotriene Biosynthesis.

FIG. 2 LTC4 synthase overall structure. a) Left, front view of LTC4 synthase protomer in ribbon representation showing helices 1 through 5. The entire LTC4 synthase polypeptide, except for the last residue (the last four in the GSH-complexed structure), can be traced in the electron density maps. Right, the homotrimer. Bound glutathione, indicating the position of the active site, in ball and stick representation. Approximate membrane positions indicated by black lines. b) Cytosolic view of the trimer, showing the position of the three active sites with loop 1 covering each binding pocket. Glutathione shown in ball and stick representation together with modelled detergent.

FIG. 3| Substrate- and lipid-protein interactions. a) Surface representation of the trimeric protein. There are ball and stick representations of carbon chains lining the protein surface. The detergent molecule is shown and underneath, a glimpse of the bound glutathione is seen. b) Cross-section from the cytosolic side of LTC4 synthase, as indicated in a), revealing the polar binding pocket of GSH and the cleft where the aliphatic co-substrate binds. Dashed bonds highlight the partial occupancy of the second pyranoside of the detergent molecule.

FIG. 4| Glutathione binding. a) Electron density map (2Fo-Fc, contoured at 3σ and phased with the apo structure before refinement) for bound glutathione shown in ball and stick representation. Interacting side chains are labeled accordingly. Chemical bonds to glutathione are drawn as dashed lines. A coordinated water molecule is shown as a sphere. b) Superposition of the active sites in the apo- and glutathione bound structures. Glutathione is shown in stick representation and the sulphate molecule from the apo-structure is indicated.

FIG. 5| The hydrophobic binding crevice and proposed schematic mechanism of substrate binding and catalysis. a) The interface between two monomers shown with interacting and bordering residues shown as sticks. A sphere shows the area where the cysteinyl sulphur is located. The bound detergent is depicted as a ball and stick model. b) Side view of the substrate binding region rotated 90° counter clockwise with respect to a). For clarity, only the monomer harbouring the Trp116′ crevice, is depicted. The removed monomer contributes hydrophobic residues to the lipid binding cleft and polar residues to glutathione. c) Schematic view of the proposed substrate binding and conjugation.

FIG. 6 Sequence alignment of the MAPEG family. Primary sequence of human (h) LTC4S aligned to other MAPEG members from mouse (m), rat (r), cow (c) and chicken (ch). Capital G indicates residues binding GSH in the structure. The conservation of these residues is highlighted. Helices indicated with corresponding helix numbers.

FIG. 7 Schematic drawing of the reaction catalyzed by LTC₄ synthase. LTA₄ and glutathione, on the left, are conjugated to form LTC₄ in a non-reversible reaction.

FIG. 8 Metal Coordination and Crystal Packing

a) Perinuclear view showing full coordination by one trimer of one metal and partial coordination of 3 metals (dots) by the hexa-histidine tag. b) Crystal symmetry, largely governed by metal clusters of in total 8 metals per dodecamer coordinating the N-terminal as shown in a).

FIG. 9 Glutathione Binding

Stereo view of active site showing electron density (2FO—FC, contoured at 3σ, phased with the apo structure before refinement) for bound glutathione shown in stick and ball representation. Interacting side chains, coloured by monomer and labelled accordingly. Chemical bonds to glutathione drawn as dashed lines.

FIG. 10 Schematic diagram of protein ligand interactions Ligplot of glutathione and interacting residues showing bond lengths and interactions as dashed lines. A dark dashed line indicates the interaction between Arg104′ and the cysteinyl sulphur.

EXAMPLE 1 Crystallisation and Structure Determination for LTC4S Materials and Methods

Imidazole, Tris base, NaCl, KCl, Triton X-100, sodium deoxycholate, S-hexylglutathione agarose, probenecid, reduced glutathione (GSH), and 2-mercaptoethanol were obtained from Sigma. Dodecyl maltoside was obtained from Anatrace.

Human LTC4S was expressed as a hexa-histidine construct in yeast. Extraction from the membrane was performed with a Triton X-100 and Triton-DOC mixture. The protein was purified using two affinity chromatography steps and finalized with a gel filtration, allowing for detergent exchange to n-dodecyl β-D-maltoside.

Cloning and Plasmid Construction

The human LTC4S cDNA (I.M.A.G.E. cDNA clone 5277851, MRC geneservice, Cambridge, UK) was subcloned into pPICZA (Invitrogen). Both the cDNA, supplemented with an Nterminal sequence encoding a His6 tag, and the vector were PCR amplified and the products were co-transformed into CaCl₂-competent E. coli (TOP10, Invitrogen), utilizing the endogenous recombinase activity of E. coli to recombine the fragments. The protein coding part of the resulting plasmid, pPICZ-hisLTC4S, was verified by DNA sequencing.

Protein Expression and Purification

The expression vector was transformed into P. pastoris KM71H cells using the Pichia EasyComp Transformation kit (Invitrogen). Recombinant cells were cultivated in baffled flasks in 2.5 L minimal yeast medium with glycerol (Invitrogen) at 27° C. When OD600 reached 8-10, the cells were resuspended in 0.5 L minimal yeast medium with 0.5% methanol. The cells were harvested after 72 h by centrifugation (2500×g, 7 min) and resuspended in 50 mM Tris-HCl, pH 7.8, 100 mM KCl and 10% glycerol. The cells were homogenised with glass beads (0.5 mm) and the slurry was filtered through nylon net filters (180 μm, Millipore) and centrifuged (1500×g, 10 min). Membrane bound proteins in the supernatant were solubilized with Triton X-100 (1%, v/v) and sodium deoxycholate (0.5%, w/v) for 1 h with stirring on ice. After centrifugation (10 000×g, 10 min) the supernatant was supplemented with 10 mM imidazole and loaded on Ni-Sepharose Fast Flow (GE Healthcare). The column was washed with buffer A (25 mM Tris-HCl, pH 7.8, 10% glycerol, 0.1% Triton X-100 and 5 mM 2-mercaptoethanol) supplemented with 20 mM imidazole and 0.1 M NaCl, followed by additional wash with buffer A containing 40 mM imidazole and 0.5 M NaCl. LTC4 synthase was eluted with 300 mM imidazole, 0.5 M NaCl and 0.1 mM GSH in buffer A. The final step of purification was performed on a column packed with 3 mL S-hexylglutathione agarose. The column was washed with buffer A, supplemented with 0.5 M NaCl and 0.1 mM GSH. Pure LTC4 synthase was eluted with 25 mM Tris-HCl, pH 7.8, 0.1% Triton X-100, 30 mM probenecid, 5 mM 2-mercaptoethanol and 0.1 mM GSH. The purified protein was either stored frozen at −20° C. or directly further polished in a buffer exchange step on a Superdex 200 16/60 (GE Healthcare.) equilibrated with 0.03% w/v DDM (w/v), 20 mM Tris pH 8.0, 300 mM NaCl and 0.5 mM TCEP. Fractions containing LTC4 synthase were concentrated to 3.1 mg ml−1 by ultrafiltration.

Crystallisation

Crystals were grown either at 4° C. or 20° C. from a 3.1 mg ml⁻¹ membrane protein solution, using sitting drop vapour diffusion technique. Crystals typically appeared after 3-4 days, reaching optimal size after approximately 7 days.

Protein solution containing 20 mM Tris pH 8.0, 300 mM NaCl, 0.03% (w/v) DDM was mixed (1:1) with reservoir solution containing either 200 mM NaCl, 100 mM Na cacodylate pH 6.5, 2 M Ammonium Sulphate (AmSO₄) for native protein; 2% PEG 400, 100 mM HEPES Na pH 7.5, 2M AmSO₄ for GSH derivative or 100 mM bis-Tris pH 5.5, 2M AmSO₄ for heavy atom soaks. For the latter, crystals were grown at 20° C. and soaked for 2 hours in 2.5 mM PtCN₄, dissolved in artificial mother liquor.

GSH derivatives were obtained by mixing equal volumes of 6 mM GSH, dissolved in mother liquor, with protein and left to soak for 24 hours at 4° C.

All crystals were transferred to their corresponding reservoir solution supplemented with 25% glycerol for cryo protection, then flash frozen in liquid nitrogen.

All X-ray data were collected on beam lines ID14-4 and ID23-2 at the European Synchrotron Radiation Facility (ESRF). Diffraction data of native and GSH soaked crystals was processed and scaled using Mosflm and SCALA while the XDS suite was used for processing and scaling of heavy atom MAD data sets.

Three highly redundant datasets to 3.2 Å were collected around the Pt LIII edge based on an X-ray fluorescence spectrum collected from the crystal. A single platinum site was located on the basis of anomalous differences observed in the peak dataset using SHELXD after local scaling in XPREP and SHELXE₂₈ confirmed the correct hand. Good experimental MAD (multiwavelength anomalous diffraction) phases were obtained using the program SHARP₂₉, resulting in an overall figure of merit (FOM) of 0.41/0.26 for the acentric/centric reflections respectively. These phases were further improved using a 75% solvent content in SOLOMON₃₀, resulting in an overall figure of merit of 0.88.

The initial map was used to model α-helices, which were in turn used together with high resolution data to assign residues with ARP/wARP₃₁ which managed to build ˜80% of the sequence. The model was further built using Coot 32 and used for molecular replacement with Phaser ₃₃ of a higher resolution apo structure and the GSH bound structure. Both protein models were built in Coot and refined using Refmac₃₄ to an R_(work)/R_(free) of 17.6/21.2% for the apo model and to 18.3/22.0% for the GSH bound structure. All crystals belonged to space group F23 with cell dimensions of approx a=b=c=170 Å and α=β=γ=90° containing one monomer per asymmetric unit having a solvent content of 80%.

All images were prepared using Pymol ₃₅ except FIG. 10 which was generated with LIGPLOT ₃₆

TABLE 8 Data collection, phasing and refinement statistics. Native 2 Native 3 Crystal 1 Native 1 Apo GSH Pt(CN)2 Data collection Space group F23 F23 F23 F23 Cell dimensions a = b = c (Å) 170.260 169.670 169.940 170.78 a = b = g (°) 90.00 90.00 90.00 90.00 Peak Inflection Remote Wavelength 0.93924 0.9390 0.8733 1.07150 1.07200 1.06888 Resolution (Å) 30.0-2.2 51.16-2.0 51.232-2.15 30.0-3.2 30.0-3.2 30.0-3.2 R_(merge) 11.2/(51.4) 8.5/(81.5) 14.1/(66.7) 15.5/(53.4) 15.4/(52.6) 14.8/(50.9) I/sI 15.6/(2.8)  16.1/(2.2)  8.8/(2.3) 14.0/(2.5)  14.6/(2.6)  13.9/(2.65) Completeness 99.8/(100)  99.8/(100)   99.8/(100)  99.5/(99.8) 99.5/(99.6) 99.5/(99.5) (%) Redundancy 7.4 7.2 5.0 6.4 6.3 6.3 Refinement Resolution (Å)   2.0-28.3   2.15-49.03 No. reflections 25914 20920 R_(work/)R_(free) 0.1756/0.2117   0.1830/0.2202   No. atoms Protein 1267 1194 Ligand/ion 53 Water 113 126 B-factors — Protein 23.7 28.0 Ligand/ion — 33.1 Water R.m.s 59.2 40.2 deviations Bond lengths 0.022 0.025 (Å) Bond angles 1.987 2.485 (°)

Results and Discussion LTC4 Architecture and Membrane Interactions

We have determined the crystal structure of the human LTC4 synthase in its apo and GSH-complexed forms, to 2.0 and 2.15 Å resolution respectively. The entire LTC4S polypeptide, except for the last residue (four last in the GSH-complexed structure), can be traced in the electron density maps. In addition, the N-terminal 6-His tag used for purification is clearly visible, and forms a unique metal coordinated cluster composed of 12 crystallographically related hexa-histidine tags (FIG. 8) coordinating 8 metals. A number of extended densities, likely to originate from ordered detergents or lipids, are seen in the maps and have been introduced into the crystallographic refinement as the detergent dodecyl maltoside (DDM) used in the purification or as tentative aliphatic chains. A notable cluster of such aliphatic chains pack against helices 1, 3 and 5, underscoring the high hydrophobicity of helix 5, where the first half is almost exclusively composed of hydrophobic residues (FIG. 3 a). In its natural membrane environment, it is plausible that helix 5 slightly changes direction to be embedded into the lipid bilayer as an interfacial surface helix.

LTC4S is composed of five long α-helices—the first four (helix 1-4) forming the transmembrane segments, while helix 5 extends out of the membrane plane (FIG. 2). The crystal structure reveals a compact trimeric protein, where a crystallographic three-fold axis relates the three subunits. Two of the three TM helix connecting loops are short (loop 2 and 3), while loop 1, connecting helix 1 and 2, is longer, constituted by 11 residues. Loop 1 folds on top of the neighbouring monomer and contributes to the subunit interaction in the trimer (FIG. 2). Helix 4 and 5 are connected by a short proline containing turn and helix 5 could also be seen as an extension of helix 4.

The active site of LTC4S, identified by a bound GSH, is buried at the interface of two adjacent monomers close to the membrane face where loop 1 is positioned. It is likely that this part of the protein faces the cytoplasmic side of the outer nuclear membrane. This would facilitate delivery and release of substrates and product, since both the preceding and following steps in the synthesis pathway are conducted on the cytosolic side of the membrane. Crystal contacts are mediated by the C-terminal helix, the N-terminal 6-His tag on the perinuclear side of the protein and also by loop 1 and 3 on the cytosolic side. The fact that the crystals contain only ˜20% protein, but still diffract to high resolution is unusual, but might be explained by the high symmetry space group (F23) and the intriguing 6-His polynuclear metal cluster which contains an internal crystallographic 322 symmetry. (FIG. 8).

The electron density maps reveals a number of extended electron densities that are likely to originate from bound detergent and lipid molecules (FIG. 2 a). In the GSH soaked structure one tentative DDM molecule is modelled close to the bound GSH, marking the active site (see below), in the crevice formed between helix 1 from one subunit and helix 3 from a neighbouring subunit. In the apo-LTC4S structure, two DDM molecules are modelled in this region.

Most of the additional aliphatic chains are also seen on the perinuclear half of the TM region and include one extended chain found in the centre of the trimer that might be important for stabilising the trimeric structure. In general, the cytoplasmic half of the molecule containing the active site pocket is more polar. The location of the active site on the cytosolic half of the enzyme is consistent with that of 5-LO, the enzyme producing the co-substrate for LTC4S, which is found in the cytosol. The topology is also consistent with that protein kinase C (Gupta N et al. FEBS Lett. (1999) 449(1):66-70) known to phosphorylate S28 of LTC4S is found in the cytosol.

The four-helix TM topology of the LTA4S is also supported by a low resolution electron diffraction projection image of LTC4S (Schmidt-Krey et al., 2004, supra). A four helix TM structure was also seen in the low resolution electron crystallography structure of the distantly related MGST1 (Holm et al 2006, supra).

Active Site Structure and Substrate Binding

The location of the active site of LTC4 synthase was revealed by a clearly bound GSH. The active site of the enzyme is buried at the interface of two adjacent monomers close to the membrane face where loop 1 is positioned, between helix 1 and 2 from one monomer and 3 and 4 from a neighbouring monomer. It is likely that this part of the protein faces the cytoplasmic side of the outer nuclear membrane. This would facilitate delivery and release of substrates and product, since both the preceding and following steps in the synthesis pathway are conducted on the cytosolic side of the membrane. GSH adopts a horseshoe shaped conformation deep in a polar pocket at the interface between helix 1 and 2 from one monomer and 3 and 4 from a neighbouring monomer (FIGS. 2 b, 3 b). The carboxylate moieties of GSH face the protein matrix, while the thiol group is directed towards the membrane layer where a DDM molecule is bound (FIG. 2 b). Polar interactions are made with GSH by residues from both subunits constituting the active site (FIGS. 4 a,b). Arg51′ and Arg30 make salt bridges to the two carboxylates of GSH, at the base of the binding pocket, effectively bending GSH and directing its thiol group towards the membrane interface where it interacts with Arg 104′ and is positioned close to a bound DDM molecule (FIGS. 3 b, 4 a). Additional polar interactions to GSH are made by Gln53, Asn55′, Glu58′, Tyr59′, Tyr93′ and Tyr97′. Several non-polar interactions are also made (Ile 27, Pro37, Leu 108′) providing a good fit for GSH into its binding pocket. For a detailed overview of the GSH-binding see FIG. 10.

The structure of LTC4S has also been determined in a GSH free apo form, where a tentative sulphate ion is found in the GSH pocket. Comparison of the GSH bound LTC4S structure with the apo-LTC4S structure reveals that only local adjustments of polar amino acid side chains are made upon GSH binding (FIG. 4 b). While the hydrophobic and aromatic residues providing interactions with GSH are in very similar positions in the two structures, most of the polar residues change conformation upon GSH binding. Loop 1 appears to at least partially cover the access of GSH to its binding pocket (FIGS. 2 b, 4 b). Therefore some flexibility of loop1 might be required during the reaction cycle, consistent with structural rearrangement of this loop upon GSH binding (FIG. 4).

Recognition of the Lipophilic LTA4 Substrate

Structures of enzymes in complexes with lipophilic substrates are rare and in fact, except for electron carriers, no direct structural information is available in the literature of an integral membrane enzymes in complex with its lipid substrate, or a good analog thereof (http://blanco.biomol.uci.edu/Membrane_Proteins_xtal.html). Crystallographic studies of LTC4S with its co-substrate LTA₄ are challenging due to the short lifetime of this epoxide containing compound (˜10 seconds). In the GSH complexed LTC4S structure, however, a lipophilic molecule is already bound in the active site region, and based on the length of the aliphatic chain and on the apparent structure of its head group, this molecule has been assigned as DDM, although the terminal sugar group is mainly disordered (FIG. 4 a). The 12-carbon chain and the first sugar group are, however, well defined in the electron density and we propose that this bound detergent might serve as a good model for the binding of LTA₄ to the enzyme as it has important structural similarities to LTA₄. The aliphatic chain binds in an elongated cavity on the enzyme lipid interface and the binding mode of this lipophilic compound positions atom 15, counted from the ω-end, on top of the GSH thiol group, consistent with LTA₄ being conjugated with GSH at this position, C6 of the LTA₄ substrate. The proposed binding canyon for LTA4 is hence constituted by a narrow elongated crevice formed by hydrophobic residues (FIG. 4 a). The hydrophobic tail of the detergent is lined by Ala20, Leu 24, Ile27 from one subunit and Tyr59′, Trp116′, Ala 112′, Leu 115′, Leu108′ and Tyr 109′, from the neighbouring subunit. Trp116′ play a key role in positioning the aliphatic chain when it forms a lid over the ω-end of the substrate. The Trp116′ pocket constitute an ingenious mode for fixing the position of the ω-end of the lipid, effectively serving as a ruler to allow the appropriate positioning of C 6 of LTA₄ at the GSH thiol. In the GSH free apo-LTC4S structure, a DDM molecule is also bound in this region of the protein but the detergent molecule is translated further down into the lipid bilayer, as compared to the DDM in the GSH complexed structure (FIG. 5 b). The effect of this translation is that the position of the detergent atom corresponding to C6 of LTA4, is now found more than 8 Å from where the GSH thiol is located in the GSH structure. Furthermore, the detergent in the apo-LTC4S structure is not wedged into the Trp 116 pocket with its ω-termini, but this termini instead sits outside the pocket. This gives further support for the fact that Trp 116 plays an important role in the alignment of the aliphatic chain of LTA₄ in the active site of LTC4S. It also suggests that GSH binding assists in the formation of an appropriate lipid binding crevice, presumably by covering charged groups in the active site and extending the interaction surface for the lipid, thereby allowing LTA₄ to enter into a productive binding mode in the active site of LTC4S.

In order to promote the GSH conjugation reaction, the nucleophilicity of the GSH thiol is most likely enhanced by the enzyme. Arg104 is ideally positioned to promote the pKa shift of the GSH thiol through its positive charge, where one of the η-nitrogens is able to mediate a polar interaction with the GSH sulphur (3.2 Å). This unusually short sulphur-nitrogen distance together with the lack of additional hydrogen bond acceptors suggest that the enzyme-bound thiol group may in fact be an anionic thiolate in the crystal structure, as suggested for the distantly related MGST-1₂₃. The GSH thiol is well positioned for a nucleophilic attack on the allylic C6 of the oxirane ring of LTA₄ ₃₇. There are no obvious acid residues situated in the active site that could provide a proton to the evolving C—O group of the substrate. It is therefore likely that the substrate oxyanion is stabilised by hydrogen bonding with the enzyme. Arg104 is located close to the expected position of the C5 of the substrate and could therefore also assist in stabilising the substrate anion. In addition, Arg31 is located on the distal side of the substrate and although it is flexible in the present structure, this residue may also assist in the stabilisation of the substrate anion. The chirality of the resulting SN2 mechanism will be defined by the productive binding of the epoxide in the active site. In the reaction, the opening of the epoxide will result in chiral inversion such that the 6S stereochemistry of the epoxide oxygen of LTA₄ will be completely converted to the 6R configuration of the resulting glutathionyl moiety of the product LTC₄.

FIG. 5 c depicts a schematic summary of the proposed mechanism for substrate binding and product generation for LTC₄ synthase. In the proposed binding scheme, GSH enters its binding pocket from the cytosol and by doing so, enables binding of LTA₄ that previously resided in the lipid membrane. The hydrophilic addition to LTA₄ enables LTC₄ to migrate out in the cytosol, perhaps depending on the flexibility of loop 1.

The structural information on LTC₄ synthase, especially on the location of the TM segments and the position of the active site residues, allows for a structure based alignment of the MAPEG family (FIG. 6). Previous sequence alignments suggest a common evolutionary origin of the human MAPEG members, where sequence conservation is low but significant in the two central TM segments, helix 2 and helix 3₁₄. Sequences in the terminal TM segments, helix 1 and 4, however, are more diverged and clear similarities can only be seen within subfamilies. In the structure based alignment, further conservation is added to the active site region of the MAPEG family by the likely alignment of helix 1. The alignment of the first three helices strongly supports that the majority of the GSH coordinating residues are conserved in all the GSH dependent MAPEG members (All MAPEG members except FLAP are known to catalyse GSH dependent reactions). Out of the 8 polar residues coordinating GSH from these helices, 5 are fully conserved in the GSH dependent enzymes, while the remaining 3 have mainly conservative amino acid substitutions. Our alignment of helix 4 is more tentative. Arg104, the critical catalytic residue proposed here is aligned with arginines predicted to reside in the N-terminal end of helix 4 of other GSH dependent MAPEG members. The position of this potential catalytic Arg in MGST-1 (Arg130) appears to be consistent with a low-resolution structure of MGST-1₁₉. While the amino acids coordinating GSH are highly conserved in the MAPEG family, the residues lining the proposed LTA₄ binding crevice are not. Although most of the corresponding residues are hydrophobic in the other families, their size and aromatic composition vary. This may indicate how the MAPEG members have evolved to recognize different lipid substrates binding in the same pocket. However, it could also suggest that lipid recognition occurs differently in the other family members, for example, MGST-1 has evolved to be highly unspecific. In addition, the nature of the head group of LTA₄ has been shown to be variable without loss of enzymatic activity_(38,39). This lack of major specificity for the head group can presumably be explained by the rather wide area in this region, which does not supply any distinct binding pocket for the carboxylate (FIGS. 3 a, 5 a).

In conclusion, it appears that the horseshoe-shaped binding mode of GSH is conserved throughout the GSH dependent MAPEG family members and, potentially, that the structural basis for GSH activation may be related. In LTC₄ synthase, the arginine at position 104 is likely to play a key role in activating the GSH thiol for a nucleophilic attack on the LTA₄ epoxide. The intriguing lipid binding pocket of LTC₄ synthase allows LTA₄ to fit into the active site by the Trp116 crevice, effectively positioning the C6 of the substrate for conjugation with GSH. It is plausible that this principle of lipid substrate recognition is primarily based on the aliphatic chain length rather than the nature of the head group. This may have some bearing also for substrate recognition in other integral membrane enzymes.

EXAMPLE 2 Computer-Based Compound Screening

Structure-based drug design utilizes the three-dimensional structure of a known target as a guide to rationally design molecules which may eventually lead to disease modifying agents, drugs. The structure of the target may be obtained through X-ray crystallography or another three-dimensional structure determination method.

Preferably, the crystals are comprised of target-ligand complexes depicting relevant binding modes and desired interactions of the putative drugs with the target. Most favorably, a series of target-ligand complexes is prepared where the complexed ligands are members of one or more series of lead compounds directed against the target. This also includes the design of ligands to diminish binding to another molecule or molecules (for example another enzyme or enzymes that shares a substrate with a target enzyme) to improve specificity to one or more desired targets.

Examination of the three-dimensional structure of one or more target-ligand complexes may lead an enhanced understanding of the binding mode of the ligands and the binding cavity of the target in the presence of the ligands. This information can be harnessed by one or more tools in medicinal chemistry or computational chemistry to form hypotheses for the modifications to the ligands which may lead to the modulation of binding affinity or improve other characteristics favorable for use as a drug.

The tools of medicinal chemistry and computational chemistry of structure-based drug design include, but are not limited to, molecular modelling, virtual screening and docking, design of focused combinatorial chemistry libraries, de novo ligand design, guides to additional candidates for three-dimensional structure determination, and rationalization of observed structure-activity relationships.

Potential modifications directed or inspired through the application of medicinal and computational tools include elaboration of a ligand to establish or modulate specific interactions with the target, removal of groups from the ligands which are deemed unimportant or detracting from desired binding affinity to the target, modification of ligand to modulate relative specificity against other targets, and elaboration of a ligand to improve its drug-like properties without producing unacceptable effects to the binding affinity to the target.

In an example, structures of small molecule compounds identified as having inhibitory activity in an enzyme activity screen can be modelled using Sybyl (Tripos Inc., 1699 South Hanley Rd., St. Louis, Mo., 63144, USA) molecular modelling software and compared with the X-ray crystallographic structure of the same or similar molecules in the active site region of the enzyme using Coot (Emsley and Cowtan, Acta Crystallographica D, 2004, 60, 2126-2132) crystallographic model-building software. Based on the comparison, changes can be made to the modelled compounds in Sybyl which are expected, on the basis of the structure comparison, to either enhance or weaken the inhibition of the enzyme. New compounds based on these models can then be synthesised and their effect in an enzyme activity screen measured. This process can be repeated, for example possibly focusing on different parts of the molecule/enzyme or different properties of the compound, as discussed above, in different rounds.

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X Ray Data

TABLE I without GSH HEADER ---XX-XXX-9- dmm COMPND --- REMARK 3 REMARK 3 REFINEMENT. REMARK 3  PROGRAM : REFMAC 5.2.0019 REMARK 3  AUTHORS : MURSHUDOV, VAGIN, DODSON REMARK 3 REMARK 3   REFINEMENT TARGET  :  MAXIMUM LIKELIHOOD REMARK 3 REMARK 3  DATA USED IN REFINEMENT. REMARK 3  RESOLUTION RANGE HIGH (ANGSTROMS) :  2.00 REMARK 3  RESOLUTION RANGE LOW (ANGSTROMS) :  28.27 REMARK 3  DATA CUTOFF (SIGMA(F)) : NONE REMARK 3  COMPLETENESS FOR RANGE (%) :  99.76 REMARK 3  NUMBER OF REFLECTIONS :  25914 REMARK 3 REMARK 3  FIT TO DATA IN REFINEMENT. REMARK 3  CROSS-VALIDATION METHOD : THROUGHOUT REMARK 3  FREE R VALUE TEST SET SELECTION : RANDOM REMARK 3  R VALUE (WORKING + TEST SET) : 0.17737 REMARK 3  R VALUE (WORKING SET) :  0.17563 REMARK 3  FREE R VALUE :  0.21171 REMARK 3  FREE R VALUE TEST SET SIZE (%) :  5.0 REMARK 3  FREE R VALUE TEST SET COUNT :  1376 REMARK 3 REMARK 3  FIT IN THE HIGHEST RESOLUTION BIN. REMARK 3  TOTAL NUMBER OF BINS USED :    20 REMARK 3  BIN RESOLUTION RANGE HIGH :   2.000 REMARK 3  BIN RESOLUTION RANGE LOW :   2.052 REMARK 3  REFLECTION IN BIN (WORKING SET) :   1882 REMARK 3  BIN COMPLETENESS (WORKING + TEST) (%) :  100.00 REMARK 3  BIN R VALUE (WORKING SET) :   0.247 REMARK 3  BIN FREE R VALUE SET COUNT :    89 REMARK 3  BIN FREE R VALUE :   0.269 REMARK 3 REMARK 3 NUMBER OF NON-HYDROGEN ATOMS USED IN REFINEMENT. REMARK 3  ALL ATOMS :   1596 REMARK 3 REMARK 3  B VALUES. REMARK 3  FROM WILSON PLOT (A**2) : NULL REMARK 3  MEAN B VALUE (OVERALL, A**2) :  30.196 REMARK 3  OVERALL ANISOTROPIC B VALUE. REMARK 3   B11 (A**2) : NULL REMARK 3   B22 (A**2) : NULL REMARK 3   B33 (A**2) : NULL REMARK 3   B12 (A**2) : NULL REMARK 3   B13 (A**2) : NULL REMARK 3   B23 (A**2) : NULL REMARK 3 REMARK 3  ESTIMATED OVERALL COORDINATE ERROR. REMARK 3  ESU BASED ON R VALUE (A): 0.102 REMARK 3  ESU BASED ON FREE R VALUE (A): 0.107 REMARK 3  ESU BASED ON MAXIMUM LIKELIHOOD (A): 0.072 REMARK 3  ESU FOR B VALUES BASED ON MAXIMUM LIKELIHOOD (A**2): 5.087 REMARK 3 REMARK 3 CORRELATION COEFFICIENTS. REMARK 3  CORRELATION COEFFICIENT FO-FC :  0.957 REMARK 3  CORRELATION COEFFICIENT FO-FC FREE :  0.945 REMARK 3 REMARK 3  RMS DEVIATIONS FROM IDEAL VALUES COUNT  RMS  WEIGHT REMARK 3  BOND LENGTHS REFINED ATOMS (A):  1514 ; 0.022 ; 0.021 REMARK 3  BOND ANGLES REFINED ATOMS (DEGREES):  2024 ; 1.987 ; 2.075 REMARK 3  TORSION ANGLES, PERIOD 1 (DEGREES):  177 ; 7.169 ; 5.000 REMARK 3  TORSION ANGLES, PERIOD 2 (DEGREES):   54 ;30.135 ;20.000 REMARK 3  TORSION ANGLES, PERIOD 3 (DEGREES):  197 ;16.738 ;15.000 REMARK 3  TORSION ANGLES, PERIOD 4 (DEGREES):   13 ;20.706 ;15.000 REMARK 3  CHIRAL-CENTER RESTRAINTS (A**3):  230 ; 0.183 ; 0.200 REMARK 3  GENERAL PLANES REFINED ATOMS (A):  1021 ; 0.009 ; 0.020 REMARK 3  NON-BONDED CONTACTS REFINED ATOMS (A):  720 ; 0.241 ; 0.200 REMARK 3  NON-BONDED TORSION REFINED ATOMS (A):  957 ; 0.317 ; 0.200 REMARK 3  H-BOND (X...Y) REFINED ATOMS (A):   79 ; 0.257 ; 0.200 REMARK 3  SYMMETRY VDW REFINED ATOMS (A):  159 ; 0.250 ; 0.200 REMARK 3  SYMMETRY H-BOND REFINED ATOMS (A):   20 ; 0.321 ; 0.200 REMARK 3 REMARK 3  ISOTROPIC THERMAL FACTOR RESTRAINTS.  COUNT  RMS  WEIGHT REMARK 3  MAIN-CHAIN BOND REFINED ATOMS (A**2):  834 ; 1.257 ; 1.500 REMARK 3  MAIN-CHAIN ANGLE REFINED ATOMS (A**2):  1289 ; 1.865 ; 2.000 REMARK 3  SIDE-CHAIN BOND REFINED ATOMS (A**2):  753 ; 3.016 ; 3.000 REMARK 3  SIDE-CHAIN ANGLE REFINED ATOMS (A**2):  723 ; 4.123 ; 4.500 REMARK 3 REMARK 3  NCS RESTRAINTS STATISTICS REMARK 3  NUMBER OF NCS GROUPS : NULL REMARK 3 REMARK 3 REMARK 3  TLS DETAILS REMARK 3  NUMBER OF TLS GROUPS  :   4 REMARK 3  ATOM RECORD CONTAINS RESIDUAL B FACTORS ONLY REMARK 3 REMARK 3  TLS GROUP  :   1 REMARK 3   NUMBER OF COMPONENTS GROUP  :    1 REMARK 3   COMPONENTS C SSSEQI TO C SSSEQI REMARK 3   RESIDUE RANGE : A   −5 A   5 REMARK 3   ORIGIN FOR THE GROUP (A):  38.5653  −48.1143  −30.3275 REMARK 3   T TENSOR REMARK 3    T11: 0.0725 T22: 0.1052 REMARK 3    T33: 0.1085 T12: −0.0606 REMARK 3    T13: 0.0711 T23: 0.0830 REMARK 3   L TENSOR REMARK 3    L11: 17.8061 L22: 2.2778 REMARK 3    L33: 10.5462 L12: 0.0569 REMARK 3    L13: −12.6791 L23: 1.8189 REMARK 3   S TENSOR REMARK 3    S11: 0.0667 S12: −0.6593 S13: −0.5618 REMARK 3    S21: −0.0684 S22: 0.0140 S23: −0.4595 REMARK 3    S31: −0.0809 S32: 0.6802 S33: −0.0807 REMARK 3 REMARK 3  TLS GROUP  :   2 REMARK 3   NUMBER OF COMPONENTS GROUP  :    1 REMARK 3   COMPONENTS C SSSEQI TO C SSSEQI REMARK 3   RESIDUE RANGE : A   6 A  112 REMARK 3   ORIGIN FOR THE GROUP (A):  15.2468  −57.8968  −10.8106 REMARK 3   T TENSOR REMARK 3    T11: 0.1017 T22: 0.1079 REMARK 3    T33: 0.0651 T12: −0.0195 REMARK 3    T13: 0.0851 T23: 0.0219 REMARK 3   L TENSOR REMARK 3    L11: 1.7350 L22: 1.3482 REMARK 3    L33: 2.1370 L12: 0.4369 REMARK 3    L13: −0.9101 L23: −0.5741 REMARK 3   S TENSOR REMARK 3    S11: −0.0534 S12: −0.2815 S13: −0.0727 REMARK 3    S21: 0.2539 S22: −0.0172 S23: 0.1277 REMARK 3    S31: 0.1175 S32: −0.0823 S33: 0.0706 REMARK 3 REMARK 3  TLS GROUP  :   3 REMARK 3   NUMBER OF COMPONENTS GROUP  :    1 REMARK 3   COMPONENTS C SSSEQI TO C SSSEQI REMARK 3   RESIDUE RANGE : A  113 A  142 REMARK 3   ORIGIN FOR THE GROUP (A):  12.8365  −48.9997  −38.6599 REMARK 3   T TENSOR REMARK 3    T11: 0.0974 T22: 0.1247 REMARK 3    T33: 0.1388 T12: −0.0022 REMARK 3    T13: −0.0214 T23: 0.0643 REMARK 3   L TENSOR REMARK 3    L11: 0.4772 L22: 1.7385 REMARK 3    L33: 15.5152 L12: 0.5613 REMARK 3    L13: −1.8713 L23: −1.4990 REMARK 3   S TENSOR REMARK 3    S11: −0.1136 S12: 0.1208 S13: 0.0559 REMARK 3    S21: −0.2355 S22: 0.0525 S23: 0.2362 REMARK 3    S31: −0.0451 S32: −0.6552 S33: 0.0611 REMARK 3 REMARK 3  TLS GROUP  :   4 REMARK 3   NUMBER OF COMPONENTS GROUP  :    1 REMARK 3   COMPONENTS C SSSEQI TO C SSSEQI REMARK 3   RESIDUE RANGE : A  143 A  149 REMARK 3   ORIGIN FOR THE GROUP (A):  11.2731  −46.1923  −66.6381 REMARK 3   T TENSOR REMARK 3    T11: 0.4358 T22: 0.4581 REMARK 3    T33: 0.4564 T12: 0.0018 REMARK 3    T13: −0.0002 T23: −0.0096 REMARK 3   L TENSOR REMARK 3    L11: 22.3722 L22: 31.1048 REMARK 3    L33: 224.2959 L12: −26.3796 REMARK 3    L13: 70.8378 L23: −83.5266 REMARK 3   S TENSOR REMARK 3    S11: 0.2737 S12: 2.4714 S13: 1.2687 REMARK 3    S21: −5.2175 S22: −3.9374 S23: −3.9650 REMARK 3    S31: 3.7824 S32: 1.4196 S33: 3.6637 REMARK 3 REMARK 3 REMARK 3  BULK SOLVENT MODELLING. REMARK 3  METHOD USED :  MASK REMARK 3  PARAMETERS FOR MASK CALCULATION REMARK 3  VDW PROBE RADIUS :  1.20 REMARK 3  ION PROBE RADIUS :  0.80 REMARK 3  SHRINKAGE RADIUS :  0.80 REMARK 3 REMARK 3  OTHER REFINEMENT REMARKS: REMARK 3  HYDROGENS HAVE BEEN ADDED IN THE RIDING POSITIONS REMARK 3 CISPEP 1 HIS A  −4 HIS A  −3 0.00 CISPEP 2 PRO A  37 PRO A  38 0.00 CISPEP 3 LEU A 143 ARG A 144 0.00 CISPEP 4 ARG A 144 THR A 145 0.00 CRYST1 169.670 169.670 169.670 90.00   90.00  90.00 F 2 3 SCALE1 0.005894 0.000000 0.000000 0.00000 SCALE2 0.000000 0.005894 0.000000 0.00000 SCALE3 0.000000 0.000000 0.005894 0.00000 ATOM 1 N ALA A −5 43.417 −56.043 −31.929 1.00 40.01 N ATOM 2 CA ALA A −5 44.846 −56.114 −31.509 1.00 40.26 C ATOM 3 CB ALA A −5 45.609 −57.239 −32.274 1.00 39.53 C ATOM 4 C ALA A −5 45.458 −54.750 −31.798 1.00 39.87 C ATOM 5 O ALA A −5 46.544 −54.674 −32.349 1.00 40.49 O ATOM 6 N HIS A −4 44.731 −53.685 −31.435 1.00 39.62 N ATOM 7 CA HIS A −4 45.061 −52.308 −31.812 1.00 37.34 C ATOM 8 CB HIS A −4 46.450 −51.924 −31.223 1.00 36.68 C ATOM 9 CG HIS A −4 47.559 −51.830 −32.233 1.00 33.52 C ATOM 10 ND1 HIS A −4 48.441 −52.864 −32.484 1.00 31.74 N ATOM 11 CE1 HIS A −4 49.312 −52.492 −33.406 1.00 31.37 C ATOM 12 NE2 HIS A −4 49.019 −51.258 −33.773 1.00 30.66 N ATOM 13 CD2 HIS A −4 47.931 −50.816 −33.047 1.00 28.76 C ATOM 14 C HIS A −4 45.004 −52.310 −33.341 1.00 37.04 C ATOM 15 O HIS A −4 45.628 −53.147 −33.953 1.00 36.99 O ATOM 16 N HIS A −3 44.287 −51.438 −34.034 1.00 36.79 N ATOM 17 CA HIS A −3 43.501 −50.265 −33.676 1.00 35.24 C ATOM 18 CB HIS A −3 42.020 −50.578 −33.563 1.00 34.83 C ATOM 19 CG HIS A −3 41.652 −51.796 −34.356 1.00 36.60 C ATOM 20 ND1 HIS A −3 41.549 −51.785 −35.734 1.00 35.20 N ATOM 21 CE1 HIS A −3 41.284 −53.008 −36.163 1.00 37.38 C ATOM 22 NE2 HIS A −3 41.227 −53.817 −35.114 1.00 35.02 N ATOM 23 CD2 HIS A −3 41.496 −53.092 −33.976 1.00 32.96 C ATOM 24 C HIS A −3 44.037 −48.993 −32.985 1.00 34.06 C ATOM 25 O HIS A −3 44.487 −48.964 −31.825 1.00 34.68 O ATOM 26 N HIS A −2 43.985 −47.955 −33.798 1.00 30.69 N ATOM 27 CA HIS A −2 44.283 −46.597 −33.397 1.00 29.38 C ATOM 28 CB HIS A −2 45.218 −46.005 −34.412 1.00 28.22 C ATOM 29 CG HIS A −2 46.542 −46.677 −34.358 1.00 26.13 C ATOM 30 ND1 HIS A −2 47.513 −46.312 −33.449 1.00 27.41 N ATOM 31 CE1 HIS A −2 48.563 −47.107 −33.584 1.00 29.67 C ATOM 32 NE2 HIS A −2 48.267 −48.026 −34.490 1.00 26.72 N ATOM 33 CD2 HIS A −2 46.995 −47.795 −34.964 1.00 24.20 C ATOM 34 C HIS A −2 43.025 −45.771 −33.151 1.00 29.66 C ATOM 35 O HIS A −2 43.067 −44.525 −33.162 1.00 29.63 O ATOM 36 N HIS A −1 41.928 −46.484 −32.937 1.00 28.29 N ATOM 37 CA HIS A −1 40.722 −45.901 −32.363 1.00 29.36 C ATOM 38 CB HIS A −1 39.833 −45.269 −33.435 1.00 29.37 C ATOM 39 CG HIS A −1 39.189 −46.282 −34.328 1.00 29.87 C ATOM 40 ND1 HIS A −1 39.843 −46.855 −35.395 1.00 27.36 N ATOM 41 CE1 HIS A −1 39.044 −47.730 −35.976 1.00 26.36 C ATOM 42 NE2 HIS A −1 37.900 −47.747 −35.318 1.00 26.52 N ATOM 43 CD2 HIS A −1 37.978 −46.878 −34.261 1.00 23.85 C ATOM 44 C HIS A −1 39.979 −47.029 −31.664 1.00 29.58 C ATOM 45 O HIS A −1 40.235 −48.223 −31.897 1.00 27.14 O ATOM 46 N HIS A 0 39.084 −46.641 −30.765 1.00 30.33 N ATOM 47 CA AHIS A 0 38.210 −47.644 −30.156 0.50 31.50 C ATOM 48 CA BHIS A 0 38.246 −47.574 −30.012 0.50 31.25 C ATOM 49 CB AHIS A 0 38.709 −48.065 −28.776 0.50 31.91 C ATOM 50 CB BHIS A 0 38.708 −47.583 −28.555 0.50 31.55 C ATOM 51 CG AHIS A 0 40.193 −48.215 −28.683 0.50 34.15 C ATOM 52 CG BHIS A 0 38.350 −46.341 −27.780 0.50 31.51 C ATOM 53 ND1 AHIS A 0 41.012 −47.196 −28.255 0.50 36.59 N ATOM 54 ND1 BHIS A 0 37.046 −45.965 −27.524 0.50 32.11 N ATOM 55 CE1 AHIS A 0 42.269 −47.606 −28.279 0.50 37.93 C ATOM 56 CE1 BHIS A 0 37.031 −44.870 −26.789 0.50 29.93 C ATOM 57 NE2 AHIS A 0 42.288 −48.862 −28.688 0.50 36.79 N ATOM 58 NE2 BHIS A 0 38.284 −44.520 −26.551 0.50 35.90 N ATOM 59 CD2 AHIS A 0 41.003 −49.268 −28.948 0.50 36.50 C ATOM 60 CD2 BHIS A 0 39.128 −45.422 −27.162 0.50 34.28 C ATOM 61 C HIS A 0 36.803 −47.073 −30.063 1.00 31.25 C ATOM 62 O HIS A 0 36.595 −45.843 −30.221 1.00 34.09 O ATOM 63 N HIS A 1 35.841 −47.958 −29.894 1.00 30.33 N ATOM 64 CA HIS A 1 34.441 −47.590 −29.816 1.00 29.97 C ATOM 65 CB HIS A 1 33.627 −48.418 −30.808 1.00 29.50 C ATOM 66 CG HIS A 1 34.011 −48.156 −32.223 1.00 27.56 C ATOM 67 ND1 HIS A 1 33.499 −47.103 −32.952 1.00 23.70 N ATOM 68 CE1 HIS A 1 34.037 −47.102 −34.155 1.00 23.80 C ATOM 69 NE2 HIS A 1 34.871 −48.123 −34.244 1.00 25.91 N ATOM 70 CD2 HIS A 1 34.888 −48.794 −33.037 1.00 20.73 C ATOM 71 C HIS A 1 33.851 −47.679 −28.403 1.00 30.10 C ATOM 72 O HIS A 1 32.636 −47.579 −28.252 1.00 30.73 O ATOM 73 N LYS A 2 34.727 −47.765 −27.395 1.00 29.69 N ATOM 74 CA LYS A 2 34.376 −47.810 −25.963 1.00 29.87 C ATOM 75 CB LYS A 2 35.618 −47.776 −25.043 1.00 29.27 C ATOM 76 CG LYS A 2 36.413 −48.999 −25.019 1.00 28.73 C ATOM 77 CD LYS A 2 37.425 −48.905 −23.891 1.00 27.66 C ATOM 78 CE LYS A 2 38.601 −48.087 −24.330 1.00 36.28 C ATOM 79 NZ LYS A 2 39.767 −48.393 −23.499 1.00 40.53 N ATOM 80 C LYS A 2 33.570 −46.603 −25.587 1.00 29.58 C ATOM 81 O LYS A 2 32.575 −46.712 −24.829 1.00 27.29 O ATOM 82 N ASP A 3 33.973 −45.452 −26.126 1.00 27.69 N ATOM 83 CA ASP A 3 33.322 −44.230 −25.730 1.00 28.51 C ATOM 84 CB ASP A 3 34.195 −42.983 −26.035 1.00 29.24 C ATOM 85 CG ASP A 3 34.690 −42.927 −27.498 1.00 34.80 C ATOM 86 OD1 ASP A 3 34.424 −43.836 −28.373 1.00 32.19 O ATOM 87 OD2 ASP A 3 35.424 −41.943 −27.755 1.00 42.71 O ATOM 88 C ASP A 3 31.928 −44.116 −26.312 1.00 27.85 C ATOM 89 O ASP A 3 31.212 −43.201 −25.976 1.00 28.12 O ATOM 90 N GLU A 4 31.526 −45.044 −27.185 1.00 26.80 N ATOM 91 CA GLU A 4 30.165 −45.057 −27.694 1.00 24.98 C ATOM 92 CB GLU A 4 30.151 −45.459 −29.168 1.00 26.58 C ATOM 93 CG GLU A 4 31.122 −44.591 −29.949 1.00 33.17 C ATOM 94 CD GLU A 4 30.987 −44.795 −31.407 1.00 40.28 C ATOM 95 OE1 GLU A 4 31.710 −45.652 −31.941 1.00 41.27 O ATOM 96 OE2 GLU A 4 30.154 −44.079 −32.011 1.00 47.02 O ATOM 97 C GLU A 4 29.233 −45.994 −26.888 1.00 23.81 C ATOM 98 O GLU A 4 28.010 −45.994 −27.128 1.00 23.71 O ATOM 99 N VAL A 5 29.768 −46.806 −25.976 1.00 20.73 N ATOM 100 CA VAL A 5 28.898 −47.787 −25.321 1.00 21.18 C ATOM 101 CB VAL A 5 29.162 −49.221 −25.939 1.00 21.98 C ATOM 102 CG1 VAL A 5 28.872 −49.207 −27.488 1.00 22.13 C ATOM 103 CG2 VAL A 5 30.626 −49.683 −25.679 1.00 20.83 C ATOM 104 C VAL A 5 29.156 −47.790 −23.847 1.00 19.14 C ATOM 105 O VAL A 5 28.709 −48.668 −23.159 1.00 19.28 O ATOM 106 N ALA A 6 29.943 −46.817 −23.364 1.00 17.79 N ATOM 107 CA ALA A 6 30.304 −46.851 −21.945 1.00 16.48 C ATOM 108 CB ALA A 6 31.438 −45.830 −21.604 1.00 15.49 C ATOM 109 C ALA A 6 29.116 −46.694 −20.974 1.00 16.52 C ATOM 110 O ALA A 6 29.153 −47.257 −19.877 1.00 14.62 O ATOM 111 N LEU A 7 28.129 −45.868 −21.330 1.00 16.27 N ATOM 112 CA LEU A 7 26.955 −45.723 −20.470 1.00 17.57 C ATOM 113 CB LEU A 7 26.023 −44.567 −20.942 1.00 16.67 C ATOM 114 CG LEU A 7 26.613 −43.149 −20.994 1.00 21.48 C ATOM 115 CD1 LEU A 7 25.575 −42.165 −21.651 1.00 21.87 C ATOM 116 CD2 LEU A 7 26.972 −42.660 −19.583 1.00 21.78 C ATOM 117 C LEU A 7 26.155 −47.054 −20.494 1.00 17.71 C ATOM 118 O LEU A 7 25.635 −47.466 −19.474 1.00 17.10 O ATOM 119 N LEU A 8 26.069 −47.688 −21.655 1.00 17.54 N ATOM 120 CA LEU A 8 25.386 −48.983 −21.746 1.00 16.81 C ATOM 121 CB LEU A 8 25.364 −49.503 −23.209 1.00 16.66 C ATOM 122 CG LEU A 8 24.740 −48.526 −24.258 1.00 17.84 C ATOM 123 CD1 LEU A 8 24.734 −49.147 −25.668 1.00 15.12 C ATOM 124 CD2 LEU A 8 23.292 −48.130 −23.831 1.00 16.84 C ATOM 125 C LEU A 8 26.131 −50.021 −20.895 1.00 17.77 C ATOM 126 O LEU A 8 25.519 −50.873 −20.247 1.00 16.05 O ATOM 127 N ALA A 9 27.462 −49.991 −20.960 1.00 16.99 N ATOM 128 CA ALA A 9 28.263 −50.932 −20.203 1.00 16.14 C ATOM 129 CB ALA A 9 29.737 −50.855 −20.583 1.00 15.06 C ATOM 130 C ALA A 9 28.086 −50.698 −18.672 1.00 15.93 C ATOM 131 O ALA A 9 28.076 −51.692 −17.894 1.00 15.13 O ATOM 132 N ALA A 10 28.006 −49.434 −18.252 1.00 15.67 N ATOM 133 CA ALA A 10 27.823 −49.094 −16.834 1.00 16.01 C ATOM 134 CB ALA A 10 28.010 −47.530 −16.585 1.00 15.78 C ATOM 135 C ALA A 10 26.428 −49.568 −16.296 1.00 16.10 C ATOM 136 O ALA A 10 26.337 −50.132 −15.228 1.00 16.67 O ATOM 137 N VAL A 11 25.386 −49.304 −17.066 1.00 15.68 N ATOM 138 CA VAL A 11 24.012 −49.773 −16.758 1.00 16.30 C ATOM 139 CB VAL A 11 22.972 −49.208 −17.703 1.00 14.94 C ATOM 140 CG1 VAL A 11 21.554 −49.864 −17.528 1.00 16.14 C ATOM 141 CG2 VAL A 11 22.882 −47.575 −17.552 1.00 15.49 C ATOM 142 C VAL A 11 24.015 −51.290 −16.733 1.00 16.92 C ATOM 143 O VAL A 11 23.349 −51.890 −15.882 1.00 16.60 O ATOM 144 N THR A 12 24.685 −51.911 −17.702 1.00 16.32 N ATOM 145 CA THR A 12 24.817 −53.378 −17.708 1.00 17.42 C ATOM 146 CB THR A 12 25.647 −53.859 −18.903 1.00 18.02 C ATOM 147 OG1 THR A 12 24.987 −53.519 −20.137 1.00 16.93 O ATOM 148 CG2 THR A 12 26.036 −55.370 −18.851 1.00 14.01 C ATOM 149 C THR A 12 25.433 −53.910 −16.409 1.00 16.73 C ATOM 150 O THR A 12 24.910 −54.894 −15.816 1.00 15.64 O ATOM 151 N LEU A 13 26.552 −53.313 −15.996 1.00 15.79 N ATOM 152 CA LEU A 13 27.221 −53.737 −14.800 1.00 16.01 C ATOM 153 CB LEU A 13 28.590 −53.047 −14.609 1.00 16.41 C ATOM 154 CG LEU A 13 29.393 −53.565 −13.388 1.00 19.68 C ATOM 155 CD1 LEU A 13 29.771 −55.020 −13.556 1.00 19.44 C ATOM 156 CD2 LEU A 13 30.713 −52.725 −13.200 1.00 19.13 C ATOM 157 C LEU A 13 26.337 −53.506 −13.570 1.00 15.89 C ATOM 158 O LEU A 13 26.323 −54.352 −12.672 1.00 14.48 O ATOM 159 N LEU A 14 25.632 −52.378 −13.502 1.00 15.35 N ATOM 160 CA ALEU A 14 24.701 −52.134 −12.396 0.50 15.61 C ATOM 161 CA BLEU A 14 24.708 −52.130 −12.403 0.50 17.49 C ATOM 162 CB ALEU A 14 23.965 −50.809 −12.565 0.50 14.81 C ATOM 163 CB BLEU A 14 24.010 −50.795 −12.601 0.50 17.49 C ATOM 164 CG ALEU A 14 22.907 −50.423 −11.509 0.50 14.03 C ATOM 165 CG BLEU A 14 24.340 −49.618 −11.680 0.50 23.49 C ATOM 166 CD1 ALEU A 14 23.472 −50.464 −10.087 0.50 14.69 C ATOM 167 CD1 BLEU A 14 23.836 −48.354 −12.361 0.50 26.02 C ATOM 168 CD2 ALEU A 14 22.393 −49.016 −11.824 0.50 13.57 C ATOM 169 CD2 BLEU A 14 23.635 −49.803 −10.304 0.50 24.03 C ATOM 170 C LEU A 14 23.638 −53.234 −12.357 1.00 16.89 C ATOM 171 O LEU A 14 23.233 −53.656 −11.277 1.00 16.93 O ATOM 172 N GLY A 15 23.162 −53.637 −13.546 1.00 17.46 N ATOM 173 CA GLY A 15 22.179 −54.730 −13.683 1.00 16.39 C ATOM 174 C GLY A 15 22.728 −56.068 −13.167 1.00 17.25 C ATOM 175 O GLY A 15 22.008 −56.795 −12.478 1.00 16.27 O ATOM 176 N VAL A 16 23.985 −56.388 −13.474 1.00 15.54 N ATOM 177 CA VAL A 16 24.635 −57.585 −12.942 1.00 16.05 C ATOM 178 CB VAL A 16 26.081 −57.768 −13.534 1.00 16.60 C ATOM 179 CG1 VAL A 16 26.889 −58.786 −12.790 1.00 13.19 C ATOM 180 CG2 VAL A 16 26.005 −58.062 −15.097 1.00 14.81 C ATOM 181 C VAL A 16 24.700 −57.497 −11.408 1.00 16.94 C ATOM 182 O VAL A 16 24.384 −58.486 −10.737 1.00 15.38 O ATOM 183 N LEU A 17 25.153 −56.345 −10.865 1.00 16.09 N ATOM 184 CA LEU A 17 25.217 −56.158 −9.422 1.00 17.41 C ATOM 185 CB LEU A 17 25.774 −54.767 −9.072 1.00 17.39 C ATOM 186 CG LEU A 17 27.252 −54.609 −9.426 1.00 18.79 C ATOM 187 CD1 LEU A 17 27.647 −53.153 −9.176 1.00 23.01 C ATOM 188 CD2 LEU A 17 28.127 −55.576 −8.560 1.00 17.11 C ATOM 189 C LEU A 17 23.847 −56.346 −8.730 1.00 16.71 C ATOM 190 O LEU A 17 23.767 −56.949 −7.656 1.00 14.14 O ATOM 191 N LEU A 18 22.801 −55.774 −9.314 1.00 16.77 N ATOM 192 CA ALEU A 18 21.424 −55.941 −8.796 0.50 16.35 C ATOM 193 CA BLEU A 18 21.461 −55.960 −8.738 0.50 17.28 C ATOM 194 CB ALEU A 18 20.433 −55.107 −9.625 0.50 16.20 C ATOM 195 CB BLEU A 18 20.446 −55.068 −9.426 0.50 17.28 C ATOM 196 CG ALEU A 18 18.964 −55.058 −9.160 0.50 15.46 C ATOM 197 CG BLEU A 18 20.350 −53.591 −9.062 0.50 19.31 C ATOM 198 CD1 ALEU A 18 18.839 −54.376 −7.795 0.50 11.79 C ATOM 199 CD1 BLEU A 18 19.355 −52.998 −10.042 0.50 16.93 C ATOM 200 CD2 ALEU A 18 18.013 −54.427 −10.216 0.50 14.53 C ATOM 201 CD2 BLEU A 18 19.894 −53.345 −7.599 0.50 18.66 C ATOM 202 C LEU A 18 20.989 −57.425 −8.810 1.00 17.19 C ATOM 203 O LEU A 18 20.348 −57.916 −7.890 1.00 16.76 O ATOM 204 N GLN A 19 21.295 −58.128 −9.897 1.00 17.14 N ATOM 205 CA GLN A 19 20.958 −59.554 −9.983 1.00 17.18 C ATOM 206 CB GLN A 19 21.254 −60.163 −11.377 1.00 16.60 C ATOM 207 CG GLN A 19 20.347 −59.642 −12.516 1.00 16.76 C ATOM 208 CD GLN A 19 18.827 −60.028 −12.267 1.00 21.75 C ATOM 209 OE1 GLN A 19 17.959 −59.196 −12.194 1.00 21.27 O ATOM 210 NE2 GLN A 19 18.581 −61.276 −12.126 1.00 18.28 N ATOM 211 C GLN A 19 21.729 −60.361 −8.946 1.00 18.44 C ATOM 212 O GLN A 19 21.171 −61.281 −8.360 1.00 16.40 O ATOM 213 N ALA A 20 23.004 −60.028 −8.737 1.00 17.03 N ATOM 214 CA ALA A 20 23.788 −60.698 −7.729 1.00 18.65 C ATOM 215 CB ALA A 20 25.240 −60.148 −7.704 1.00 18.11 C ATOM 216 C ALA A 20 23.144 −60.456 −6.357 1.00 19.31 C ATOM 217 O ALA A 20 23.092 −61.366 −5.503 1.00 18.87 O ATOM 218 N TYR A 21 22.699 −59.225 −6.130 1.00 18.33 N ATOM 219 CA TYR A 21 22.041 −58.885 −4.880 1.00 19.08 C ATOM 220 CB TYR A 21 21.742 −57.387 −4.855 1.00 19.27 C ATOM 221 CG TYR A 21 20.869 −56.985 −3.692 1.00 22.24 C ATOM 222 CD1 TYR A 21 21.394 −56.910 −2.401 1.00 23.86 C ATOM 223 CE1 TYR A 21 20.586 −56.526 −1.340 1.00 25.39 C ATOM 224 CZ TYR A 21 19.262 −56.203 −1.595 1.00 24.30 C ATOM 225 OH TYR A 21 18.446 −55.826 −0.571 1.00 27.49 O ATOM 226 CE2 TYR A 21 18.739 −56.245 −2.867 1.00 25.76 C ATOM 227 CD2 TYR A 21 19.539 −56.628 −3.892 1.00 22.26 C ATOM 228 C TYR A 21 20.750 −59.717 −4.647 1.00 18.54 C ATOM 229 O TYR A 21 20.509 −60.207 −3.535 1.00 18.86 O ATOM 230 N PHE A 22 19.959 −59.901 −5.699 1.00 18.09 N ATOM 231 CA PHE A 22 18.702 −60.656 −5.615 1.00 17.87 C ATOM 232 CB PHE A 22 17.942 −60.678 −6.944 1.00 16.55 C ATOM 233 CG PHE A 22 17.414 −59.362 −7.367 1.00 18.68 C ATOM 234 CD1 PHE A 22 17.160 −58.359 −6.431 1.00 16.52 C ATOM 235 CE1 PHE A 22 16.657 −57.094 −6.817 1.00 17.66 C ATOM 236 CZ PHE A 22 16.413 −56.823 −8.173 1.00 18.35 C ATOM 237 CE2 PHE A 22 16.700 −57.824 −9.142 1.00 19.95 C ATOM 238 CD2 PHE A 22 17.186 −59.104 −8.729 1.00 18.06 C ATOM 239 C PHE A 22 19.062 −62.094 −5.227 1.00 17.94 C ATOM 240 O PHE A 22 18.402 −62.692 −4.375 1.00 16.29 O ATOM 241 N SER A 23 20.119 −62.627 −5.841 1.00 17.48 N ATOM 242 CA ASER A 23 20.609 −63.977 −5.526 0.50 18.22 C ATOM 243 CA BSER A 23 20.607 −63.979 −5.524 0.50 18.14 C ATOM 244 CB ASER A 23 21.743 −64.373 −6.496 0.50 18.07 C ATOM 245 CB BSER A 23 21.764 −64.390 −6.459 0.50 17.96 C ATOM 246 OG ASER A 23 21.172 −64.782 −7.725 0.50 17.88 O ATOM 247 OG BSER A 23 21.969 −65.784 −6.334 0.50 17.40 O ATOM 248 C SER A 23 21.052 −64.132 −4.074 1.00 18.29 C ATOM 249 O SER A 23 20.715 −65.143 −3.407 1.00 18.63 O ATOM 250 N LEU A 24 21.797 −63.150 −3.578 1.00 18.16 N ATOM 251 CA LEU A 24 22.211 −63.166 −2.191 1.00 20.24 C ATOM 252 CB LEU A 24 23.208 −62.051 −1.887 1.00 21.40 C ATOM 253 CG LEU A 24 24.537 −62.161 −2.669 1.00 25.52 C ATOM 254 CD1 LEU A 24 25.348 −60.826 −2.669 1.00 27.61 C ATOM 255 CD2 LEU A 24 25.433 −63.346 −2.181 1.00 28.16 C ATOM 256 C LEU A 24 20.993 −63.080 −1.279 1.00 20.87 C ATOM 257 O LEU A 24 20.974 −63.698 −0.204 1.00 19.35 O ATOM 258 N GLN A 25 19.970 −62.331 −1.688 1.00 20.20 N ATOM 259 CA GLN A 25 18.769 −62.243 −0.834 1.00 20.86 C ATOM 260 CB GLN A 25 17.844 −61.147 −1.343 1.00 20.63 C ATOM 261 CG GLN A 25 18.363 −59.767 −1.108 1.00 26.30 C ATOM 262 CD GLN A 25 18.336 −59.415 0.352 1.00 31.82 C ATOM 263 OE1 GLN A 25 19.368 −59.242 0.972 1.00 36.59 O ATOM 264 NE2 GLN A 25 17.145 −59.354 0.922 1.00 37.03 N ATOM 265 C GLN A 25 18.014 −63.599 −0.763 1.00 19.55 C ATOM 266 O GLN A 25 17.436 −63.957 0.273 1.00 19.83 O ATOM 267 N VAL A 26 18.004 −64.344 −1.865 1.00 18.97 N ATOM 268 CA VAL A 26 17.426 −65.679 −1.853 1.00 19.01 C ATOM 269 CB VAL A 26 17.356 −66.299 −3.264 1.00 19.68 C ATOM 270 CG1 VAL A 26 16.870 −67.745 −3.190 1.00 18.47 C ATOM 271 CG2 VAL A 26 16.433 −65.468 −4.130 1.00 19.44 C ATOM 212 C VAL A 26 18.209 −66.598 −0.922 1.00 19.18 C ATOM 273 O VAL A 26 17.603 −67.351 −0.176 1.00 17.84 O ATOM 274 N ILE A 27 19.540 −66.574 −0.994 1.00 18.77 N ATOM 275 CA ILE A 27 20.368 −67.361 −0.081 1.00 18.90 C ATOM 276 CB ILE A 27 21.872 −67.186 −0.396 1.00 19.36 C ATOM 277 CG1 ILE A 27 22.168 −67.738 −1.801 1.00 19.09 C ATOM 278 CD1 ILE A 27 23.527 −67.372 −2.345 1.00 21.97 C ATOM 279 CG2 ILE A 27 22.768 −67.923 0.683 1.00 16.77 C ATOM 280 C ILE A 27 20.088 −66.972 1.381 1.00 20.52 C ATOM 281 O ILE A 27 20.019 −67.814 2.279 1.00 18.92 O ATOM 282 N SER A 28 19.923 −65.676 1.611 1.00 21.21 N ATOM 283 CA SER A 28 19.598 −65.189 2.930 1.00 22.97 C ATOM 284 CB SER A 28 19.706 −63.658 2.950 1.00 22.02 C ATOM 285 OG SER A 28 19.162 −63.196 4.183 1.00 29.00 O ATOM 286 C SER A 28 18.203 −65.679 3.388 1.00 22.89 C ATOM 287 O SER A 28 18.035 −66.082 4.523 1.00 22.64 O ATOM 288 N ALA A 29 17.214 −65.659 2.493 1.00 23.91 N ATOM 289 CA ALA A 29 15.865 −66.183 2.797 1.00 23.51 C ATOM 290 CB ALA A 29 14.866 −65.824 1.680 1.00 22.99 C ATOM 291 C ALA A 29 15.858 −67.681 3.051 1.00 24.00 C ATOM 292 O ALA A 29 15.073 −68.156 3.864 1.00 23.89 O ATOM 293 N ARG A 30 16.697 −68.436 2.340 1.00 24.05 N ATOM 294 CA ARG A 30 16.889 −69.872 2.601 1.00 24.83 C ATOM 295 CB ARG A 30 17.953 −70.466 1.666 1.00 24.79 C ATOM 296 CG ARG A 30 17.442 −71.056 0.403 1.00 23.58 C ATOM 297 CD ARG A 30 18.611 −71.522 −0.501 1.00 25.95 C ATOM 298 NE ARG A 30 18.140 −71.735 −1.879 1.00 31.89 N ATOM 299 CZ ARG A 30 17.282 −72.709 −2.245 1.00 32.74 C ATOM 300 NH1 ARG A 30 16.809 −73.552 −1.329 1.00 26.90 N ATOM 301 NH2 ARG A 30 16.886 −72.852 −3.520 1.00 26.35 N ATOM 302 C ARG A 30 17.296 −70.172 4.053 1.00 26.73 C ATOM 303 O ARG A 30 16.859 −71.188 4.631 1.00 25.68 O ATOM 304 N ARG A 31 18.136 −69.312 4.642 1.00 28.09 N ATOM 305 CA ARG A 31 18.486 −69.426 6.072 1.00 29.61 C ATOM 306 CB ARG A 31 19.806 −68.732 6.380 1.00 30.78 C ATOM 307 CG ARG A 31 20.959 −69.299 5.571 1.00 35.56 C ATOM 308 CD ARG A 31 21.813 −68.181 4.962 1.00 44.64 C ATOM 309 NE ARG A 31 23.081 −68.659 4.386 1.00 49.92 N ATOM 310 CZ ARG A 31 24.024 −67.860 3.879 1.00 54.18 C ATOM 311 NE1 ARG A 31 23.844 −66.530 3.854 1.00 55.03 N ATOM 312 NH2 ARG A 31 25.143 −68.386 3.373 1.00 55.84 N ATOM 313 C ARG A 31 17.375 −68.914 6.995 1.00 29.48 C ATOM 314 O ARG A 31 16.919 −69.643 7.879 1.00 28.43 O ATOM 315 N ALA A 32 16.911 −67.680 6.783 1.00 29.12 N ATOM 316 CA ALA A 32 15.800 −67.176 7.593 1.00 29.17 C ATOM 317 CB ALA A 32 15.349 −65.806 7.126 1.00 28.95 C ATOM 318 C ALA A 32 14.622 −68.163 7.628 1.00 29.78 C ATOM 319 O ALA A 32 14.097 −68.471 8.699 1.00 29.40 O ATOM 320 N PHE A 33 14.234 −68.696 6.468 1.00 30.14 N ATOM 321 CA PHE A 33 13.040 −69.536 6.403 1.00 30.08 C ATOM 322 CB PHE A 33 12.127 −69.061 5.289 1.00 30.34 C ATOM 323 CG PHE A 33 11.816 −67.626 5.409 1.00 31.02 C ATOM 324 CD1 PHE A 33 11.058 −67.178 6.483 1.00 32.95 C ATOM 325 CE1 PHE A 33 10.794 −65.818 6.646 1.00 34.66 C ATOM 326 CZ PHE A 33 11.288 −64.893 5.742 1.00 33.75 C ATOM 327 CE2 PHE A 33 12.076 −65.336 4.648 1.00 34.48 C ATOM 328 CD2 PHE A 33 12.334 −66.702 4.504 1.00 32.19 C ATOM 329 C PHE A 33 13.322 −71.010 6.344 1.00 29.65 C ATOM 330 O PHE A 33 12.400 −71.813 6.127 1.00 29.19 O ATOM 331 N ARG A 34 14.579 −71.366 6.615 1.00 29.06 N ATOM 332 CA ARG A 34 14.995 −72.774 6.706 1.00 28.59 C ATOM 333 CB ARG A 34 14.435 −73.427 7.996 1.00 29.80 C ATOM 334 CG ARG A 34 14.347 −72.512 9.225 1.00 33.40 C ATOM 335 CD ARG A 34 15.642 −72.504 10.040 1.00 40.97 C ATOM 336 NE ARG A 34 15.448 −71.941 11.394 1.00 46.03 N ATOM 337 CZ ARG A 34 15.778 −70.690 11.743 1.00 48.13 C ATOM 338 NH1 ARG A 34 16.318 −69.853 10.843 1.00 46.71 N ATOM 339 NH2 ARG A 34 15.567 −70.270 12.991 1.00 49.30 N ATOM 340 C ARG A 34 14.549 −73.586 5.482 1.00 27.84 C ATOM 341 O ARG A 34 13.721 −74.488 5.613 1.00 27.01 O ATOM 342 N VAL A 35 15.062 −73.239 4.285 1.00 26.72 N ATOM 343 CA VAL A 35 14.850 −74.044 3.081 1.00 25.93 C ATOM 344 CB VAL A 35 14.109 −73.224 1.967 1.00 25.70 C ATOM 345 CG1 VAL A 35 13.853 −74.088 0.734 1.00 24.14 C ATOM 346 CG2 VAL A 35 12.807 −72.636 2.511 1.00 26.15 C ATOM 347 C VAL A 35 16.180 −74.571 2.530 1.00 26.42 C ATOM 348 O VAL A 35 17.033 −73.785 2.055 1.00 28.00 O ATOM 349 N SER A 36 16.358 −75.879 2.485 1.00 25.58 N ATOM 350 CA SER A 36 17.659 −76.397 2.045 1.00 27.44 C ATOM 351 CB SER A 36 18.135 −77.585 2.923 1.00 27.60 C ATOM 352 OG SER A 36 17.100 −78.531 3.105 1.00 31.58 O ATOM 353 C SER A 36 17.644 −76.781 0.566 1.00 27.25 C ATOM 354 O SER A 36 16.652 −77.349 0.110 1.00 26.82 O ATOM 355 N PRO A 37 18.722 −76.440 −0.183 1.00 27.91 N ATOM 356 CA PRO A 37 18.980 −76.878 −1.579 1.00 27.78 C ATOM 357 CB PRO A 37 20.368 −76.318 −1.862 1.00 27.43 C ATOM 358 CG PRO A 37 20.467 −75.142 −0.958 1.00 27.76 C ATOM 359 CD PRO A 37 19.786 −75.539 0.296 1.00 27.85 C ATOM 360 C PRO A 37 18.976 −78.431 −1.697 1.00 28.57 C ATOM 361 O PRO A 37 19.380 −79.080 −0.755 1.00 28.21 O ATOM 362 N PRO A 38 18.481 −79.006 −2.827 1.00 29.15 N ATOM 363 CA PRO A 38 17.946 −78.317 −4.032 1.00 29.69 C ATOM 364 CB PRO A 38 17.825 −79.449 −5.044 1.00 29.10 C ATOM 365 CG PRO A 38 17.599 −80.684 −4.242 1.00 29.23 C ATOM 366 CD PRO A 38 18.331 −80.478 −2.915 1.00 29.05 C ATOM 367 C PRO A 38 16.579 −77.858 −3.557 1.00 31.15 C ATOM 368 O PRO A 38 16.329 −77.953 −2.357 1.00 31.21 O ATOM 369 N LEU A 39 15.629 −77.422 −4.358 1.00 31.64 N ATOM 370 CA LEU A 39 14.314 −77.307 −3.600 1.00 31.36 C ATOM 371 CB LEU A 39 14.358 −78.099 −2.298 1.00 32.57 C ATOM 372 CG LEU A 39 13.205 −78.765 −1.538 1.00 33.34 C ATOM 373 CD1 LEU A 39 13.595 −79.057 −0.071 1.00 37.71 C ATOM 374 CD2 LEU A 39 12.846 −80.105 −2.226 1.00 37.19 C ATOM 375 C LEU A 39 14.044 −75.881 −3.248 1.00 30.76 C ATOM 376 O LEU A 39 14.863 −75.168 −2.653 1.00 30.37 O ATOM 377 N THR A 40 12.889 −75.453 −3.697 1.00 30.19 N ATOM 378 CA THR A 40 12.610 −74.057 −3.883 1.00 29.53 C ATOM 379 CB THR A 40 12.688 −73.773 −5.367 1.00 30.60 C ATOM 380 OG1 THR A 40 11.937 −74.791 −6.056 1.00 31.63 O ATOM 381 CG2 THR A 40 14.141 −73.849 −5.799 1.00 29.67 C ATOM 382 C THR A 40 11.203 −73.800 −3.360 1.00 28.92 C ATOM 383 O THR A 40 10.597 −72.784 −3.659 1.00 29.15 O ATOM 384 N THR A 41 10.704 −74.765 −2.583 1.00 27.72 N ATOM 385 CA THR A 41 9.417 −74.650 −1.909 1.00 27.48 C ATOM 386 CB THR A 41 8.502 −75.882 −2.175 1.00 27.00 C ATOM 387 OG1 THR A 41 9.214 −77.087 −1.892 1.00 27.66 O ATOM 388 CG2 THR A 41 8.072 −75.910 −3.621 1.00 29.36 C ATOM 389 C THR A 41 9.699 −74.492 −0.431 1.00 25.77 C ATOM 390 O THR A 41 10.661 −75.046 0.065 1.00 25.46 O ATOM 391 N GLY A 42 8.905 −73.683 0.252 1.00 24.99 N ATOM 392 CA GLY A 42 8.945 −73.595 1.708 1.00 23.67 C ATOM 393 C GLY A 42 7.875 −72.582 2.070 1.00 23.48 C ATOM 394 O GLY A 42 6.894 −72.444 1.352 1.00 22.56 O ATOM 395 N PRO A 43 8.072 −71.841 3.160 1.00 23.65 N ATOM 396 CA PRO A 43 7.110 −70.819 3.581 1.00 24.08 C ATOM 397 CB PRO A 43 7.832 −70.125 4.742 1.00 24.25 C ATOM 398 CG PRO A 43 8.783 −71.149 5.257 1.00 25.08 C ATOM 399 CD PRO A 43 9.233 −71.924 4.060 1.00 23.63 C ATOM 400 C PRO A 43 6.783 −69.793 2.479 1.00 24.09 C ATOM 401 O PRO A 43 7.610 −69.534 1.594 1.00 23.76 O ATOM 402 N PRO A 44 5.575 −69.205 2.535 1.00 24.85 N ATOM 403 CA PRO A 44 5.142 −68.124 1.623 1.00 24.39 C ATOM 404 CB PRO A 44 3.905 −67.536 2.312 1.00 24.28 C ATOM 405 CG PRO A 44 3.355 −68.696 3.171 1.00 24.88 C ATOM 406 CD PRO A 44 4.533 −69.582 3.522 1.00 24.64 C ATOM 407 C PRO A 44 6.208 −67.048 1.468 1.00 25.03 C ATOM 408 O PRO A 44 6.509 −66.629 0.337 1.00 24.73 O ATOM 409 N GLU A 45 6.785 −66.592 2.577 1.00 25.54 N ATOM 410 CA GLU A 45 7.791 −65.505 2.508 1.00 26.37 C ATOM 411 CB GLU A 45 8.148 −65.013 3.911 1.00 26.87 C ATOM 412 CG GLU A 45 7.986 −66.063 5.051 1.00 33.53 C ATOM 413 CD GLU A 45 6.539 −66.308 5.538 1.00 35.80 C ATOM 414 OE1 GLU A 45 5.895 −65.375 6.067 1.00 40.36 O ATOM 415 OE2 GLU A 45 6.050 −67.448 5.397 1.00 35.30 O ATOM 416 C GLU A 45 9.019 −65.920 1.707 1.00 25.19 C ATOM 417 O GLU A 45 9.577 −65.130 0.919 1.00 26.91 O ATOM 418 N PHE A 46 9.416 −67.180 1.840 1.00 24.09 N ATOM 419 CA PHE A 46 10.514 −67.686 1.041 1.00 22.77 C ATOM 420 CB PHE A 46 11.040 −69.058 1.513 1.00 22.24 C ATOM 421 CG PHE A 46 12.039 −69.620 0.560 1.00 21.92 C ATOM 422 CD1 PHE A 46 13.354 −69.131 0.550 1.00 22.58 C ATOM 423 CE1 PHE A 46 14.297 −69.571 −0.403 1.00 24.84 C ATOM 424 CZ PHE A 46 13.918 −70.488 −1.397 1.00 21.95 C ATOM 425 CE2 PHE A 46 12.570 −70.965 −1.407 1.00 24.69 C ATOM 426 CD2 PHE A 46 11.648 −70.513 −0.432 1.00 22.55 C ATOM 427 C PHE A 46 10.116 −67.746 −0.438 1.00 21.60 C ATOM 428 O PHE A 46 10.870 −67.304 −1.291 1.00 21.09 O ATOM 429 N GLU A 47 8.937 −68.283 −0.736 1.00 20.53 N ATOM 430 CA GLU A 47 8.510 −68.514 −2.110 1.00 21.35 C ATOM 431 CB GLU A 47 7.255 −69.428 −2.217 1.00 20.97 C ATOM 432 CG GLU A 47 7.552 −70.837 −1.600 1.00 24.76 C ATOM 433 CD GLU A 47 6.517 −71.960 −1.915 1.00 25.54 C ATOM 434 OE1 GLU A 47 5.538 −71.723 −2.666 1.00 31.53 O ATOM 435 OE2 GLU A 47 6.720 −73.111 −1.429 1.00 30.90 O ATOM 436 C GLU A 47 8.346 −67.187 −2.869 1.00 20.28 C ATOM 437 O GLU A 47 8.696 −67.121 −4.063 1.00 20.94 O ATOM 438 N ARG A 48 7.895 −66.129 −2.182 1.00 18.14 N ATOM 439 CA ARG A 48 7.808 −64.822 −2.830 1.00 18.29 C ATOM 440 CB ARG A 48 7.068 −63.815 −1.947 1.00 17.43 C ATOM 441 CG ARG A 48 5.519 −64.068 −1.806 1.00 18.36 C ATOM 442 CD ARG A 48 4.802 −62.867 −1.200 1.00 19.00 C ATOM 443 NE ARG A 48 5.470 −62.390 0.030 1.00 17.46 N ATOM 444 CZ ARG A 48 5.165 −62.827 1.253 1.00 17.53 C ATOM 445 NH1 ARG A 48 4.236 −63.780 1.421 1.00 14.56 N ATOM 446 NH2 ARG A 48 5.825 −62.346 2.290 1.00 18.95 N ATOM 447 C ARG A 48 9.216 −64.278 −3.237 1.00 17.89 C ATOM 448 O ARG A 48 9.375 −63.673 −4.285 1.00 16.60 O ATOM 449 N VAL A 49 10.203 −64.442 −2.354 1.00 18.24 N ATOM 450 CA VAL A 49 11.547 −63.897 −2.571 1.00 18.62 C ATOM 451 CB VAL A 49 12.432 −64.045 −1.288 1.00 18.71 C ATOM 452 CG1 VAL A 49 13.930 −63.668 −1.646 1.00 18.08 C ATOM 453 CG2 VAL A 49 11.927 −63.102 −0.190 1.00 18.68 C ATOM 454 C VAL A 49 12.171 −64.709 −3.724 1.00 18.95 C ATOM 455 O VAL A 49 12.825 −64.140 −4.621 1.00 18.18 O ATOM 456 N TYR A 50 11.986 −66.033 −3.654 1.00 17.64 N ATOM 457 CA TYR A 50 12.406 −66.948 −4.717 1.00 19.43 C ATOM 458 CB TYR A 50 12.079 −68.396 −4.342 1.00 19.93 C ATOM 459 CG TYR A 50 12.435 −69.317 −5.462 1.00 22.07 C ATOM 460 CD1 TYR A 50 13.766 −69.562 −5.777 1.00 23.24 C ATOM 461 CE1 TYR A 50 14.114 −70.378 −6.836 1.00 24.35 C ATOM 462 CZ TYR A 50 13.114 −70.971 −7.580 1.00 25.00 C ATOM 463 OH TYR A 50 13.447 −71.822 −8.637 1.00 27.98 O ATOM 464 CE2 TYR A 50 11.782 −70.758 −7.284 1.00 22.26 C ATOM 465 CD2 TYR A 50 11.448 −69.920 −6.225 1.00 22.60 C ATOM 466 C TYR A 50 11.821 −66.571 −6.080 1.00 19.23 C ATOM 467 O TYR A 50 12.557 −66.461 −7.110 1.00 19.32 O ATOM 468 N ARG A 51 10.513 −66.341 −6.099 1.00 19.18 N ATOM 469 CA ARG A 51 9.817 −66.052 −7.324 1.00 19.97 C ATOM 470 CB ARG A 51 8.293 −66.173 −7.181 1.00 21.05 C ATOM 471 CG ARG A 51 7.498 −65.862 −8.506 1.00 26.10 C ATOM 472 CD ARG A 51 7.675 −67.005 −9.547 1.00 31.39 C ATOM 473 NE ARG A 51 7.726 −68.297 −8.867 1.00 31.38 N ATOM 474 CZ ARG A 51 8.413 −69.344 −9.311 1.00 34.69 C ATOM 475 NH1 ARG A 51 9.100 −69.263 −10.450 1.00 22.44 N ATOM 476 NH2 ARG A 51 8.410 −70.486 −8.607 1.00 35.43 N ATOM 477 C ARG A 51 10.232 −64.688 −7.880 1.00 20.18 C ATOM 478 O ARG A 51 10.372 −64.567 −9.088 1.00 18.68 O ATOM 479 N ALA A 52 10.427 −63.683 −7.002 1.00 17.84 N ATOM 480 CA ALA A 52 10.853 −62.354 −7.440 1.00 17.20 C ATOM 481 CB ALA A 52 10.935 −61.413 −6.249 1.00 15.92 C ATOM 482 C ALA A 52 12.237 −62.461 −8.187 1.00 15.68 C ATOM 483 O ALA A 52 12.430 −61.854 −9.232 1.00 15.58 O ATOM 484 N GLN A 53 13.135 −63.289 −7.650 1.00 16.26 N ATOM 485 CA GLN A 53 14.501 −63.483 −8.212 1.00 17.49 C ATOM 486 CB GLN A 53 15.395 −64.268 −7.244 1.00 17.15 C ATOM 487 CG GLN A 53 16.792 −64.600 −7.845 1.00 19.66 C ATOM 488 CD GLN A 53 16.789 −65.983 −8.427 1.00 24.83 C ATOM 489 OE1 GLN A 53 16.560 −66.937 −7.715 1.00 33.39 O ATOM 490 NE2 GLN A 53 16.992 −66.106 −9.732 1.00 30.94 N ATOM 491 C GLN A 53 14.383 −64.212 −9.519 1.00 17.09 C ATOM 492 O GLN A 53 14.971 −63.794 −10.524 1.00 15.97 O ATOM 493 N VAL A 54 13.587 −65.286 −9.542 1.00 16.48 N ATOM 494 CA VAL A 54 13.379 −66.003 −10.791 1.00 18.24 C ATOM 495 CB VAL A 54 12.432 −67.201 −10.631 1.00 17.35 C ATOM 496 CG1 VAL A 54 12.072 −67.761 −12.023 1.00 19.79 C ATOM 497 CG2 VAL A 54 13.117 −68.271 −9.764 1.00 17.59 C ATOM 498 C VAL A 54 12.842 −65.065 −11.901 1.00 18.53 C ATOM 499 O VAL A 54 13.329 −65.148 −13.050 1.00 18.60 O ATOM 500 N ASN A 55 11.817 −64.241 −11.594 1.00 17.49 N ATOM 501 CA AASN A 55 11.243 −63.380 −12.616 0.50 17.51 C ATOM 502 CA BASN A 55 11.191 −63.292 −12.587 0.50 18.24 C ATOM 503 CB AASN A 55 9.941 −62.756 −12.090 0.50 16.84 C ATOM 504 CB BASN A 55 10.002 −62.467 −11.963 0.50 18.04 C ATOM 505 CG AASN A 55 8.828 −63.784 −11.879 0.50 16.39 C ATOM 506 CG BASN A 55 8.947 −61.909 −13.033 0.50 20.63 C ATOM 507 OD1 AASN A 55 8.862 −64.899 −12.396 0.50 16.04 O ATOM 508 OD1 BASN A 55 8.830 −60.662 −13.333 0.50 20.83 O ATOM 509 ND2 AASN A 55 7.843 −63.406 −11.110 0.50 15.88 N ATOM 510 ND2 BASN A 55 8.163 −62.839 −13.587 0.50 22.68 N ATOM 511 C ASN A 55 12.249 −62.307 −13.108 1.00 17.59 C ATOM 512 O ASN A 55 12.361 −62.023 −14.346 1.00 18.17 O ATOM 513 N CYS A 56 12.999 −61.726 −12.179 1.00 16.96 N ATOM 514 CA CYS A 56 14.022 −60.745 −12.544 1.00 18.32 C ATOM 515 CB CYS A 56 14.714 −60.116 −11.337 1.00 16.70 C ATOM 516 SG CYS A 56 13.524 −59.032 −10.424 1.00 20.36 S ATOM 517 C CYS A 56 15.054 −61.423 −13.451 1.00 18.71 C ATOM 518 O CYS A 56 15.399 −60.855 −14.454 1.00 19.05 O ATOM 519 N SER A 57 15.461 −62.652 −13.114 1.00 17.88 N ATOM 520 CA SER A 57 16.442 −63.388 −13.912 1.00 19.79 C ATOM 521 CB SER A 57 16.829 −64.712 −13.222 1.00 19.31 C ATOM 522 OG SER A 57 17.644 −64.400 −12.105 1.00 23.46 O ATOM 523 C SER A 57 15.954 −63.681 −15.313 1.00 19.97 C ATOM 524 O SER A 57 16.719 −63.627 −16.256 1.00 18.51 O ATOM 525 N GLU A 58 14.686 −64.063 −15.430 1.00 19.38 N ATOM 526 CA GLU A 58 14.071 −64.300 −16.712 1.00 22.71 C ATOM 527 CB GLU A 58 12.650 −64.809 −16.454 1.00 22.29 C ATOM 528 CG GLU A 58 11.610 −64.725 −17.615 1.00 28.06 C ATOM 529 CD GLU A 58 10.119 −64.921 −17.129 1.00 29.82 C ATOM 530 OE1 GLU A 58 9.855 −65.434 −15.974 1.00 37.40 O ATOM 531 OE2 GLU A 58 9.194 −64.583 −17.921 1.00 40.41 O ATOM 532 C GLU A 58 14.054 −63.071 −17.636 1.00 20.72 C ATOM 533 O GLU A 58 14.265 −63.194 −18.856 1.00 20.19 O ATOM 534 N TYR A 59 13.719 −61.914 −17.084 1.00 18.16 N ATOM 535 CA TYR A 59 13.655 −60.716 −17.892 1.00 19.28 C ATOM 536 CB TYR A 59 12.731 −59.697 −17.263 1.00 18.76 C ATOM 537 CG TYR A 59 11.300 −59.947 −17.621 1.00 23.86 C ATOM 538 CD1 TYR A 59 10.738 −59.328 −18.728 1.00 26.67 C ATOM 539 CE1 TYR A 59 9.406 −59.580 −19.092 1.00 27.52 C ATOM 540 CZ TYR A 59 8.641 −60.410 −18.323 1.00 27.28 C ATOM 541 OH TYR A 59 7.343 −60.578 −18.686 1.00 30.09 O ATOM 542 CE2 TYR A 59 9.149 −61.038 −17.165 1.00 26.90 C ATOM 543 CD2 TYR A 59 10.517 −60.823 −16.857 1.00 23.94 C ATOM 544 C TYR A 59 15.046 −60.078 −18.139 1.00 17.75 C ATOM 545 O TYR A 59 15.174 −59.191 −18.944 1.00 18.12 O ATOM 546 N PHE A 60 16.030 −60.482 −17.366 1.00 16.65 N ATOM 547 CA PHE A 60 17.314 −59.788 −17.398 1.00 17.08 C ATOM 548 CB PHE A 60 18.228 −60.264 −16.249 1.00 16.84 C ATOM 549 CG PHE A 60 19.545 −59.491 −16.175 1.00 21.47 C ATOM 550 CD1 PHE A 60 19.551 −58.134 −15.840 1.00 24.35 C ATOM 551 CE1 PHE A 60 20.732 −57.409 −15.771 1.00 23.58 C ATOM 552 CZ PHE A 60 21.932 −58.048 −16.025 1.00 20.33 C ATOM 553 CE2 PHE A 60 21.965 −59.374 −16.383 1.00 24.02 C ATOM 554 CD2 PHE A 60 20.725 −60.106 −16.465 1.00 22.80 C ATOM 555 C PHE A 60 18.020 −59.878 −18.804 1.00 17.03 C ATOM 556 O PHE A 60 18.512 −58.852 −19.285 1.00 16.38 O ATOM 557 N PRO A 61 18.004 −61.050 −19.474 1.00 16.53 N ATOM 558 CA PRO A 61 18.582 −60.994 −20.837 1.00 18.85 C ATOM 559 CB PRO A 61 18.604 −62.474 −21.297 1.00 17.13 C ATOM 560 CG PRO A 61 18.397 −63.332 −19.981 1.00 16.10 C ATOM 561 CD PRO A 61 17.627 −62.422 −19.073 1.00 15.15 C ATOM 562 C PRO A 61 17.781 −60.119 −21.831 1.00 18.43 C ATOM 563 O PRO A 61 18.359 −59.572 −22.792 1.00 18.09 O ATOM 564 N LEU A 62 16.476 −60.001 −21.599 1.00 18.07 N ATOM 565 CA ALEU A 62 15.622 −59.205 −22.475 0.50 18.05 C ATOM 566 CA BLEU A 62 15.629 −59.215 −22.477 0.50 18.30 C ATOM 567 CB ALEU A 62 14.116 −59.376 −22.165 0.50 17.27 C ATOM 568 CB BLEU A 62 14.129 −59.446 −22.183 0.50 17.43 C ATOM 569 CG ALEU A 62 13.359 −60.517 −22.828 0.50 17.98 C ATOM 570 CG BLEU A 62 13.720 −60.919 −22.126 0.50 18.62 C ATOM 571 CD1 ALEU A 62 13.903 −61.893 −22.336 0.50 17.72 C ATOM 572 CD1 BLEU A 62 12.234 −61.075 −21.700 0.50 16.30 C ATOM 573 CD2 ALEU A 62 11.819 −60.393 −22.550 0.50 17.18 C ATOM 574 CD2 BLEU A 62 14.022 −61.581 −23.482 0.50 17.70 C ATOM 575 C LEU A 62 15.992 −57.756 −22.289 1.00 18.54 C ATOM 576 O LEU A 62 16.108 −57.011 −23.263 1.00 17.70 O ATOM 577 N PHE A 63 16.141 −57.360 −21.022 1.00 16.90 N ATOM 578 CA PHE A 63 16.551 −56.048 −20.688 1.00 17.56 C ATOM 579 CB PHE A 63 16.629 −55.862 −19.186 1.00 17.32 C ATOM 580 CG PHE A 63 17.464 −54.659 −18.799 1.00 21.52 C ATOM 581 CD1 PHE A 63 17.041 −53.382 −19.147 1.00 23.75 C ATOM 582 CE1 PHE A 63 17.791 −52.293 −18.805 1.00 25.51 C ATOM 583 CZ PHE A 63 18.946 −52.456 −18.076 1.00 19.58 C ATOM 584 CE2 PHE A 63 19.398 −53.627 −17.761 1.00 24.95 C ATOM 585 CD2 PHE A 63 18.619 −54.804 −18.113 1.00 21.83 C ATOM 586 C PHE A 63 17.943 −55.717 −21.350 1.00 17.30 C ATOM 587 O PHE A 63 18.081 −54.698 −22.037 1.00 18.03 O ATOM 588 N LEU A 64 18.922 −56.588 −21.158 1.00 17.10 N ATOM 589 CA LEU A 64 20.249 −56.352 −21.725 1.00 19.18 C ATOM 590 CB LEU A 64 21.157 −57.518 −21.361 1.00 20.25 C ATOM 591 CG LEU A 64 21.639 −57.357 −19.858 1.00 24.98 C ATOM 592 CD1 LEU A 64 22.854 −58.226 −19.728 1.00 30.26 C ATOM 593 CD2 LEU A 64 22.032 −55.828 −19.381 1.00 26.42 C ATOM 594 C LEU A 64 20.205 −56.251 −23.257 1.00 17.32 C ATOM 595 O LEU A 64 20.827 −55.367 −23.826 1.00 15.36 O ATOM 596 N ALA A 65 19.530 −57.205 −23.908 1.00 14.59 N ATOM 597 CA ALA A 65 19.500 −57.230 −25.382 1.00 16.84 C ATOM 598 CB ALA A 65 18.605 −58.408 −25.903 1.00 15.91 C ATOM 599 C ALA A 65 18.894 −55.878 −25.861 1.00 17.29 C ATOM 600 O ALA A 65 19.428 −55.269 −26.783 1.00 16.12 O ATOM 601 N THR A 66 17.787 −55.436 −25.245 1.00 16.24 N ATOM 602 CA ATHR A 66 17.085 −54.275 −25.751 0.50 16.49 C ATOM 603 CA BTHR A 66 17.091 −54.262 −25.768 0.50 18.16 C ATOM 604 CB ATHR A 66 15.639 −54.219 −25.219 0.50 16.54 C ATOM 605 CB BTHR A 66 15.623 −54.159 −25.288 0.50 18.45 C ATOM 606 OG1 ATHR A 66 15.054 −55.525 −25.308 0.50 14.40 O ATOM 607 OG1 BTHR A 66 15.598 −53.940 −23.872 0.50 23.96 O ATOM 608 CG2 ATHR A 66 14.840 −53.304 −26.054 0.50 13.47 C ATOM 609 CG2 BTHR A 66 14.850 −55.451 −25.654 0.50 17.71 C ATOM 610 C THR A 66 17.852 −52.983 −25.432 1.00 17.60 C ATOM 611 O THR A 66 17.928 −52.039 −26.281 1.00 18.07 O ATOM 612 N LEU A 67 18.452 −52.955 −24.258 1.00 17.19 N ATOM 613 CA LEU A 67 19.299 −51.826 −23.859 1.00 16.58 C ATOM 614 CB LEU A 67 20.005 −52.135 −22.551 1.00 16.20 C ATOM 615 CG LEU A 67 21.108 −51.166 −22.030 1.00 17.33 C ATOM 616 CD1 LEU A 67 20.488 −49.743 −21.679 1.00 16.06 C ATOM 617 CD2 LEU A 67 21.873 −51.749 −20.853 1.00 18.05 C ATOM 618 C LEU A 67 20.384 −51.580 −24.949 1.00 17.71 C ATOM 619 O LEU A 67 20.625 −50.431 −25.353 1.00 17.60 O ATOM 620 N TRP A 68 21.107 −52.644 −25.319 1.00 15.96 N ATOM 621 CA TRP A 68 22.205 −52.529 −26.278 1.00 16.78 C ATOM 622 CB TRP A 68 23.062 −53.830 −26.262 1.00 17.05 C ATOM 623 CG TRP A 68 23.991 −53.781 −25.072 1.00 18.39 C ATOM 624 CD1 TRP A 68 23.699 −54.162 −23.769 1.00 19.58 C ATOM 625 NE1 TRP A 68 24.777 −53.912 −22.967 1.00 18.86 N ATOM 626 CE2 TRP A 68 25.775 −53.323 −23.697 1.00 17.20 C ATOM 627 CD2 TRP A 68 25.299 −53.181 −25.031 1.00 18.42 C ATOM 628 CE3 TRP A 68 26.151 −52.601 −26.019 1.00 20.65 C ATOM 629 CZ3 TRP A 68 27.431 −52.170 −25.618 1.00 19.83 C ATOM 630 CH2 TRP A 68 27.866 −52.310 −24.257 1.00 17.97 C ATOM 631 CZ2 TRP A 68 27.036 −52.854 −23.279 1.00 15.13 C ATOM 632 C TRP A 68 21.691 −52.135 −27.683 1.00 17.12 C ATOM 633 O TRP A 68 22.282 −51.250 −28.355 1.00 17.75 O ATOM 634 N VAL A 69 20.611 −52.755 −28.134 1.00 17.13 N ATOM 635 CA VAL A 69 20.089 −52.422 −29.466 1.00 15.80 C ATOM 636 CB VAL A 69 18.978 −53.437 −29.958 1.00 16.41 C ATOM 637 CG1 VAL A 69 18.389 −52.940 −31.309 1.00 14.45 C ATOM 638 CG2 VAL A 69 19.587 −54.918 −30.115 1.00 14.25 C ATOM 639 C VAL A 69 19.558 −50.995 −29.473 1.00 16.34 C ATOM 640 O VAL A 69 19.897 −50.190 −30.373 1.00 16.09 O ATOM 641 N ALA A 70 18.795 −50.620 −28.457 1.00 16.18 N ATOM 642 CA ALA A 70 18.322 −49.236 −28.359 1.00 16.59 C ATOM 643 CB ALA A 70 17.292 −49.022 −27.202 1.00 15.43 C ATOM 644 C ALA A 70 19.524 −48.259 −28.250 1.00 17.63 C ATOM 645 O ALA A 70 19.488 −47.171 −28.847 1.00 16.15 O ATOM 646 N GLY A 71 20.552 −48.617 −27.476 1.00 17.57 N ATOM 647 CA GLY A 71 21.633 −47.669 −27.236 1.00 17.83 C ATOM 648 C GLY A 71 22.510 −47.450 −28.479 1.00 19.25 C ATOM 649 O GLY A 71 23.059 −46.371 −28.671 1.00 20.19 O ATOM 650 N ILE A 72 22.635 −48.482 −29.296 1.00 19.23 N ATOM 651 CA AILE A 72 23.436 −48.393 −30.511 0.50 19.12 C ATOM 652 CA BILE A 72 23.421 −48.451 −30.530 0.50 19.30 C ATOM 653 CB AILE A 72 24.036 −49.785 −30.871 0.50 19.29 C ATOM 654 CB BILE A 72 23.875 −49.933 −30.876 0.50 19.24 C ATOM 655 CG1 AILE A 72 24.957 −50.247 −29.729 0.50 19.85 C ATOM 656 CG1 BILE A 72 24.767 −50.461 −29.740 0.50 21.26 C ATOM 657 CD1 AILE A 72 25.481 −51.642 −29.945 0.50 17.89 C ATOM 658 CD1 BILE A 72 26.064 −49.729 −29.586 0.50 22.94 C ATOM 659 CG2 AILE A 72 24.757 −49.748 −32.234 0.50 21.32 C ATOM 660 CG2 BILE A 72 24.551 −50.049 −32.259 0.50 21.24 C ATOM 661 C ILE A 72 22.624 −47.830 −31.687 1.00 18.16 C ATOM 662 O ILE A 72 23.164 −47.034 −32.485 1.00 18.23 O ATOM 663 N PHE A 73 21.349 −48.190 −32.817 1.00 17.72 N ATOM 664 CA PHE A 73 20.570 −47.769 −33.014 1.00 18.09 C ATOM 665 CB PHE A 73 19.699 −48.942 −33.564 1.00 17.61 C ATOM 666 CG PHE A 73 20.535 −49.944 −34.310 1.00 18.14 C ATOM 667 CD1 PHE A 73 20.775 −49.756 −35.678 1.00 17.06 C ATOM 668 CE1 PHE A 73 21.596 −50.670 −36.419 1.00 19.45 C ATOM 669 CZ PHE A 73 22.259 −51.718 −35.738 1.00 17.54 C ATOM 670 CE2 PHE A 73 22.093 −51.883 −34.328 1.00 19.22 C ATOM 671 CD2 PHE A 73 21.224 −50.966 −33.615 1.00 17.60 C ATOM 672 C PHE A 73 19.753 −46.491 −32.795 1.00 19.06 C ATOM 673 O PHE A 73 19.325 −45.855 −33.776 1.00 19.49 O ATOM 674 N PHE A 74 19.468 −46.143 −31.545 1.00 17.92 N ATOM 675 CA PHE A 74 18.567 −45.017 −31.312 1.00 18.88 C ATOM 676 CB PHE A 74 17.286 −45.372 −30.483 1.00 18.92 C ATOM 677 CG PHE A 74 16.403 −44.178 −30.278 1.00 21.26 C ATOM 678 CD1 PHE A 74 15.452 −43.848 −31.227 1.00 18.16 C ATOM 679 CE1 PHE A 74 14.635 −42.687 −31.085 1.00 23.68 C ATOM 680 CZ PHE A 74 14.830 −41.837 −30.005 1.00 18.69 C ATOM 681 CE2 PHE A 74 15.764 −42.156 −29.019 1.00 20.85 C ATOM 682 CD2 PHE A 74 16.559 −43.345 −29.147 1.00 22.36 C ATOM 683 C PHE A 74 19.359 −43.868 −30.671 1.00 19.91 C ATOM 684 O PHE A 74 19.571 −42.826 −31.322 1.00 19.59 O ATOM 685 N HIS A 75 19.847 −44.049 −29.421 1.00 17.73 N ATOM 686 CA HIS A 75 20.561 −42.964 −28.708 1.00 17.98 C ATOM 687 CB HIS A 75 19.591 −41.844 −28.301 1.00 18.20 C ATOM 688 CG HIS A 75 20.251 −40.633 −27.705 1.00 20.13 C ATOM 689 ND1 HIS A 75 20.387 −40.452 −26.345 1.00 19.72 N ATOM 690 CE1 HIS A 75 21.005 −39.300 −26.107 1.00 21.80 C ATOM 691 NE2 HIS A 75 21.249 −38.708 −27.269 1.00 19.17 N ATOM 692 CD2 HIS A 75 20.799 −39.520 −28.288 1.00 22.06 C ATOM 693 C HIS A 75 21.108 −43.601 −27.456 1.00 19.24 C ATOM 694 O HIS A 75 20.307 −44.145 −26.645 1.00 17.21 O ATOM 695 N GLU A 76 22.408 −43.451 −27.222 1.00 18.92 N ATOM 696 CA GLU A 76 23.028 −44.115 −26.080 1.00 20.30 C ATOM 697 CB GLU A 76 24.554 −43.999 −26.070 1.00 20.71 C ATOM 698 CG GLU A 76 25.095 −45.064 −25.104 1.00 20.24 C ATOM 699 CD GLU A 76 26.505 −44.772 −24.564 1.00 26.40 C ATOM 700 OE1 GLU A 76 27.141 −43.750 −24.865 1.00 20.94 O ATOM 701 OE2 GLU A 76 27.032 −45.619 −23.889 1.00 22.43 O ATOM 702 C GLU A 76 22.481 −43.617 −24.744 1.00 22.00 C ATOM 703 O GLU A 76 22.127 −44.438 −23.872 1.00 19.31 O ATOM 704 N GLY A 77 22.470 −42.275 −24.560 1.00 18.68 N ATOM 705 CA GLY A 77 21.991 −41.657 −23.331 1.00 20.17 C ATOM 706 C GLY A 77 20.542 −42.015 −22.977 1.00 20.69 C ATOM 707 O GLY A 77 20.233 −42.338 −21.809 1.00 18.70 O ATOM 708 N ALA A 78 19.636 −41.856 −23.951 1.00 20.03 N ATOM 709 CA ALA A 78 18.229 −42.204 −23.728 1.00 19.13 C ATOM 710 CB ALA A 78 17.390 −41.956 −25.019 1.00 18.42 C ATOM 711 C ALA A 78 18.094 −43.694 −23.277 1.00 19.09 C ATOM 712 O ALA A 78 17.273 −43.990 −22.394 1.00 18.88 O ATOM 713 N ALA A 79 18.811 −44.605 −23.941 1.00 17.24 N ATOM 714 CA ALA A 79 18.690 −46.040 −23.694 1.00 18.98 C ATOM 715 CB ALA A 79 19.520 −46.852 −24.712 1.00 16.12 C ATOM 716 C ALA A 79 19.193 −46.296 −22.256 1.00 19.35 C ATOM 717 O ALA A 79 18.562 −47.018 −21.493 1.00 17.91 O ATOM 718 N ALA A 80 20.308 −45.661 −21.894 1.00 19.28 N ATOM 719 CA ALA A 80 20.904 −45.847 −20.572 1.00 19.17 C ATOM 720 CB ALA A 80 22.267 −45.170 −20.490 1.00 19.18 C ATOM 721 C ALA A 80 19.961 −45.307 −19.481 1.00 20.41 C ATOM 722 O ALA A 80 19.808 −45.969 −18.429 1.00 18.59 O ATOM 723 N LEU A 81 19.299 −44.164 −19.727 1.00 20.48 N ATOM 724 CA ALEU A 81 18.362 −43.581 −18.756 0.50 20.31 C ATOM 725 CA BLEU A 81 18.374 −43.598 −18.738 0.50 20.74 C ATOM 726 CB ALEU A 81 17.846 −42.205 −19.235 0.50 20.84 C ATOM 727 CB BLEU A 81 17.895 −42.193 −19.152 0.50 21.74 C ATOM 728 CG ALEU A 81 16.961 −41.487 −18.213 0.50 21.25 C ATOM 729 CG BLEU A 81 18.856 −41.043 −18.838 0.50 23.64 C ATOM 730 CD1 ALEU A 81 17.748 −41.264 −16.909 0.50 21.72 C ATOM 731 CD1 BLEU A 81 18.247 −39.683 −19.256 0.50 26.66 C ATOM 732 CD2 ALEU A 81 16.382 −40.154 −18.738 0.50 20.22 C ATOM 733 CD2 BLEU A 81 19.273 −41.055 −17.353 0.50 26.64 C ATOM 734 C LEU A 81 17.191 −44.526 −18.545 1.00 20.66 C ATOM 735 O LEU A 81 16.793 −44.804 −17.415 1.00 19.85 O ATOM 736 N CYS A 82 16.640 −45.025 −19.651 1.00 21.19 N ATOM 737 CA ACYS A 82 15.521 −45.972 −19.573 0.50 20.47 C ATOM 738 CA BCYS A 82 15.521 −45.926 −19.562 0.50 22.15 C ATOM 739 CB ACYS A 82 15.060 −46.422 −20.950 0.50 20.52 C ATOM 740 CB BCYS A 82 15.015 −46.191 −20.972 0.50 22.49 C ATOM 741 SG ACYS A 82 14.219 −45.219 −21.911 0.50 16.00 S ATOM 742 SG BCYS A 82 13.427 −46.924 −21.064 0.50 28.68 S ATOM 743 C CYS A 82 15.971 −47.228 −18.829 1.00 21.10 C ATOM 744 O CYS A 82 15.219 −47.789 −18.035 1.00 21.11 O ATOM 745 N GLY A 83 17.200 −47.672 −19.104 1.00 21.21 N ATOM 746 CA GLY A 83 17.796 −48.814 −18.408 1.00 19.98 C ATOM 747 C GLY A 83 17.875 −48.634 −16.895 1.00 20.49 C ATOM 748 O GLY A 83 17.550 −49.564 −16.120 1.00 19.00 O ATOM 749 N LEU A 84 18.291 −47.445 −16.459 1.00 20.81 N ATOM 750 CA ALEU A 84 18.331 −47.116 −15.020 0.50 20.55 C ATOM 751 CA BLEU A 84 18.322 −47.086 −15.043 0.50 21.28 C ATOM 752 CB ALEU A 84 18.934 −45.734 −14.767 0.50 20.70 C ATOM 753 CB BLEU A 84 18.824 −45.664 −14.914 0.50 22.11 C ATOM 754 CG ALEU A 84 20.399 −45.516 −15.112 0.50 16.86 C ATOM 755 CG BLEU A 84 19.428 −45.297 −13.591 0.50 21.14 C ATOM 756 CD1 ALEU A 84 20.705 −44.026 −14.878 0.50 15.98 C ATOM 757 CD1 BLEU A 84 20.548 −46.316 −13.252 0.50 22.18 C ATOM 758 CD2 ALEU A 84 21.264 −46.391 −14.256 0.50 16.03 C ATOM 759 CD2 BLEU A 84 19.947 −43.868 −13.748 0.50 25.13 C ATOM 760 C LEU A 84 16.942 −47.154 −14.375 1.00 22.12 C ATOM 761 O LEU A 84 16.780 −47.699 −13.264 1.00 20.87 O ATOM 762 N VAL A 85 15.969 −46.566 −15.055 1.00 20.92 N ATOM 763 CA VAL A 85 14.598 −46.584 −14.585 1.00 21.52 C ATOM 764 CB VAL A 85 13.678 −45.769 −15.556 1.00 21.13 C ATOM 765 CG1 VAL A 85 12.215 −46.002 −15.196 1.00 22.01 C ATOM 766 CG2 VAL A 85 14.041 −44.266 −15.486 1.00 21.32 C ATOM 767 C VAL A 85 14.080 −48.042 −14.482 1.00 19.58 C ATOM 768 O VAL A 85 13.444 −48.401 −13.507 1.00 18.76 O ATOM 769 N TYR A 86 14.366 −48.867 −15.496 1.00 18.46 N ATOM 770 CA TYR A 86 13.984 −50.292 −15.451 1.00 18.04 C ATOM 771 CB TYR A 86 14.445 −50.999 −16.750 1.00 17.97 C ATOM 772 CG TYR A 86 14.235 −52.487 −16.675 1.00 17.31 C ATOM 773 CD1 TYR A 86 12.950 −53.046 −16.892 1.00 17.48 C ATOM 774 CE1 TYR A 86 12.724 −54.431 −16.799 1.00 19.08 C ATOM 775 CZ TYR A 86 13.762 −55.232 −16.405 1.00 17.56 C ATOM 776 OH TYR A 86 13.568 −56.602 −16.275 1.00 18.91 O ATOM 777 CE2 TYR A 86 15.047 −54.700 −16.142 1.00 18.55 C ATOM 778 CD2 TYR A 86 15.278 −53.329 −16.268 1.00 15.18 C ATOM 779 C TYR A 86 14.609 −50.995 −14.226 1.00 18.86 C ATOM 780 O TYR A 86 13.933 −51.744 −13.480 1.00 16.48 O ATOM 781 N LEU A 87 15.914 −50.802 −14.045 1.00 17.24 N ATOM 782 CA LEU A 87 16.581 −51.474 −12.947 1.00 18.96 C ATOM 783 CB LEU A 87 18.103 −51.270 −13.039 1.00 17.19 C ATOM 784 CG LEU A 87 18.752 −52.019 −14.252 1.00 19.85 C ATOM 785 CD1 LEU A 87 20.275 −51.618 −14.296 1.00 17.06 C ATOM 786 CD2 LEU A 87 18.554 −53.597 −14.221 1.00 17.77 C ATOM 787 C LEU A 87 16.093 −51.031 −11.540 1.00 19.19 C ATOM 788 O LEU A 87 15.971 −51.870 −10.629 1.00 19.36 O ATOM 789 N PHE A 88 15.903 −49.733 −11.360 1.00 17.43 N ATOM 790 CA PHE A 88 15.302 −49.234 −10.120 1.00 20.02 C ATOM 791 CB PHE A 88 15.242 −47.702 −10.128 1.00 20.93 C ATOM 792 CG PHE A 88 14.782 −47.131 −8.810 1.00 26.16 C ATOM 793 CD1 PHE A 88 15.341 −47.584 −7.608 1.00 29.81 C ATOM 794 CE1 PHE A 88 14.913 −47.067 −6.370 1.00 32.36 C ATOM 795 CZ PHE A 88 13.932 −46.088 −6.332 1.00 28.54 C ATOM 796 CE2 PHE A 88 13.356 −45.636 −7.507 1.00 30.57 C ATOM 797 CD2 PHE A 88 13.787 −46.157 −8.749 1.00 32.31 C ATOM 798 C PHE A 88 13.899 −49.812 −9.884 1.00 18.74 C ATOM 799 O PHE A 88 13.556 −50.179 −8.773 1.00 18.39 O ATOM 800 N ALA A 89 13.093 −49.866 −10.940 1.00 19.03 N ATOM 801 CA ALA A 89 11.801 −50.497 −10.885 1.00 19.00 C ATOM 802 CB ALA A 89 10.988 −50.290 −12.207 1.00 18.02 C ATOM 803 C ALA A 89 11.912 −51.968 −10.499 1.00 19.43 C ATOM 804 O ALA A 89 11.092 −52.410 −9.705 1.00 19.80 O ATOM 805 N ARG A 90 12.899 −52.706 −11.042 1.00 18.14 N ATOM 806 CA ARG A 90 13.061 −54.099 −10.671 1.00 17.88 C ATOM 807 CB ARG A 90 14.020 −54.851 −11.588 1.00 16.67 C ATOM 808 CG ARG A 90 13.362 −55.176 −12.931 1.00 17.81 C ATOM 809 CD ARG A 90 12.329 −56.235 −12.639 1.00 21.67 C ATOM 810 NE ARG A 90 11.629 −56.725 −13.814 1.00 21.80 N ATOM 811 CZ ARG A 90 10.778 −57.759 −13.798 1.00 23.73 C ATOM 812 NH1 ARG A 90 10.586 −58.469 −12.696 1.00 26.84 N ATOM 813 NH2 ARG A 90 10.147 −58.132 −14.917 1.00 28.04 N ATOM 814 C ARG A 90 13.496 −54.276 −9.213 1.00 17.36 C ATOM 815 O ARG A 90 13.073 −55.240 −8.593 1.00 17.83 O ATOM 816 N LEU A 91 14.372 −53.404 −8.716 1.00 17.15 N ATOM 817 CA LEU A 91 14.734 −53.365 −7.308 1.00 17.59 C ATOM 818 CB LEU A 91 15.761 −52.272 −7.001 1.00 17.32 C ATOM 819 CG LEU A 91 16.100 −52.060 −5.499 1.00 20.87 C ATOM 820 CD1 LEU A 91 16.577 −53.397 −4.813 1.00 19.29 C ATOM 821 CD2 LEU A 91 17.184 −51.001 −5.297 1.00 19.59 C ATOM 822 C LEU A 91 13.474 −53.170 −6.397 1.00 18.14 C ATOM 823 O LEU A 91 13.311 −53.901 −5.401 1.00 16.88 O ATOM 824 N ARG A 92 12.613 −52.201 −6.747 1.00 17.24 N ATOM 825 CA ARG A 92 11.374 −51.943 −5.980 1.00 19.42 C ATOM 826 CB ARG A 92 10.675 −50.669 −6.469 1.00 19.24 C ATOM 827 CG ARG A 92 11.494 −49.394 −6.194 1.00 21.86 C ATOM 828 CD ARG A 92 10.623 −48.083 −6.361 1.00 24.79 C ATOM 829 NE ARG A 92 9.774 −48.029 −7.583 1.00 34.60 N ATOM 830 CZ ARG A 92 10.178 −47.615 −8.798 1.00 35.55 C ATOM 831 NH1 ARG A 92 11.433 −47.250 −9.005 1.00 36.03 N ATOM 832 NH2 ARG A 92 9.325 −47.563 −9.812 1.00 38.08 N ATOM 833 C ARG A 92 10.429 −53.142 −6.110 1.00 18.23 C ATOM 834 O ARG A 92 9.799 −53.542 −5.139 1.00 17.11 O ATOM 835 N TYR A 93 10.346 −53.733 −7.303 1.00 15.50 N ATOM 836 CA TYR A 93 9.538 −54.955 −7.502 1.00 16.06 C ATOM 837 CB TYR A 93 9.711 −55.405 −8.970 1.00 15.77 C ATOM 838 CG TYR A 93 9.227 −56.828 −9.260 1.00 15.29 C ATOM 839 CD1 TYR A 93 7.864 −57.082 −9.563 1.00 15.92 C ATOM 840 CE1 TYR A 93 7.400 −58.395 −9.819 1.00 15.43 C ATOM 841 CZ TYR A 93 8.309 −59.447 −9.815 1.00 16.21 C ATOM 842 OH TYR A 93 7.857 −60.705 −10.136 1.00 18.01 O ATOM 843 CE2 TYR A 93 9.638 −59.243 −9.529 1.00 15.76 C ATOM 844 CD2 TYR A 93 10.116 −57.906 −9.270 1.00 15.19 C ATOM 845 C TYR A 93 9.977 −56.096 −6.543 1.00 16.71 C ATOM 846 O TYR A 93 9.161 −56.769 −5.872 1.00 16.64 O ATOM 847 N PHE A 94 11.277 −56.369 −6.549 1.00 17.13 N ATOM 848 CA PHE A 94 11.841 −57.432 −5.675 1.00 17.54 C ATOM 849 CB PHE A 94 13.356 −57.500 −5.868 1.00 18.07 C ATOM 850 CG PHE A 94 13.980 −58.638 −5.153 1.00 17.06 C ATOM 851 CD1 PHE A 94 14.087 −59.878 −5.784 1.00 20.58 C ATOM 852 CE1 PHE A 94 14.713 −60.987 −5.106 1.00 21.45 C ATOM 853 CZ PHE A 94 15.148 −60.800 −3.786 1.00 20.36 C ATOM 854 CE2 PHE A 94 15.048 −59.556 −3.165 1.00 21.74 C ATOM 855 CD2 PHE A 94 14.465 −58.473 −3.842 1.00 19.21 C ATOM 856 C PHE A 94 11.561 −57.205 −4.195 1.00 18.80 C ATOM 857 O PHE A 94 11.087 −58.117 −3.490 1.00 17.16 O ATOM 858 N GLN A 95 11.892 −55.999 −3.723 1.00 19.26 N ATOM 859 CA GLN A 95 11.555 −55.546 −2.341 1.00 21.36 C ATOM 860 CB GLN A 95 12.069 −54.112 −2.119 1.00 21.28 C ATOM 861 CG GLN A 95 13.606 −54.041 −2.241 1.00 24.86 C ATOM 862 CD GLN A 95 14.153 −52.624 −2.124 1.00 25.49 C ATOM 863 OE1 GLN A 95 13.545 −51.641 −2.598 1.00 29.36 O ATOM 864 NE2 GLN A 95 15.321 −52.516 −1.501 1.00 33.43 N ATOM 865 C GLN A 95 10.057 −55.589 −1.981 1.00 20.51 C ATOM 866 O GLN A 95 9.703 −56.042 −0.895 1.00 19.37 O ATOM 867 N GLY A 96 9.196 −55.152 −2.909 1.00 20.23 N ATOM 868 CA GLY A 96 7.735 −55.219 −2.724 1.00 19.67 C ATOM 869 C GLY A 96 7.279 −56.661 −2.575 1.00 18.78 C ATOM 870 O GLY A 96 6.615 −57.030 −1.609 1.00 18.34 O ATOM 871 N TYR A 97 7.653 −57.466 −3.563 1.00 17.46 N ATOM 872 CA TYR A 97 7.246 −58.852 −3.674 1.00 17.69 C ATOM 873 CB TYR A 97 7.879 −59.508 −4.946 1.00 17.70 C ATOM 874 CG TYR A 97 7.122 −60.683 −5.537 1.00 18.83 C ATOM 875 CD1 TYR A 97 6.134 −61.358 −4.803 1.00 20.76 C ATOM 876 CE1 TYR A 97 5.424 −62.435 −5.353 1.00 19.31 C ATOM 877 CZ TYR A 97 5.754 −62.912 −6.599 1.00 20.19 C ATOM 878 OH TYR A 97 5.063 −63.998 −7.107 1.00 21.90 O ATOM 879 CE2 TYR A 97 6.762 −62.279 −7.363 1.00 17.58 C ATOM 880 CD2 TYR A 97 7.451 −61.186 −6.816 1.00 18.08 C ATOM 881 C TYR A 97 7.680 −59.597 −2.412 1.00 17.60 C ATOM 882 O TYR A 97 6.902 −60.400 −1.879 1.00 16.26 O ATOM 883 N ALA A 98 8.904 −59.346 −1.928 1.00 17.96 N ATOM 884 CA ALA A 98 9.366 −60.011 −0.697 1.00 19.75 C ATOM 885 CB ALA A 98 10.796 −59.562 −0.346 1.00 19.79 C ATOM 886 C ALA A 98 8.372 −59.767 0.502 1.00 20.41 C ATOM 887 O ALA A 98 8.128 −60.678 1.345 1.00 21.07 O ATOM 888 N ARG A 99 7.777 −58.568 0.551 1.00 19.91 N ATOM 889 CA ARG A 99 6.821 −58.186 1.614 1.00 21.60 C ATOM 890 CB ARG A 99 6.761 −56.663 1.835 1.00 21.87 C ATOM 891 CG ARG A 99 8.070 −56.072 2.335 1.00 25.72 C ATOM 892 CD ARG A 99 8.051 −54.516 2.237 1.00 26.32 C ATOM 893 NE ARG A 99 6.967 −53.939 3.035 1.00 35.80 N ATOM 894 CZ ARG A 99 6.330 −52.802 2.734 1.00 39.54 C ATOM 895 NH1 ARG A 99 6.666 −52.122 1.636 1.00 40.73 N ATOM 896 NH2 ARG A 99 5.351 −52.349 3.528 1.00 39.32 N ATOM 897 C ARG A 99 5.418 −58.683 1.312 1.00 19.55 C ATOM 898 O ARG A 99 4.750 −59.212 2.197 1.00 18.16 O ATOM 899 N SER A 100 4.988 −58.563 0.051 1.00 18.32 N ATOM 900 CA ASER A 100 3.640 −58.976 −0.318 0.50 17.53 C ATOM 901 CA BSER A 100 3.687 −59.100 −0.332 0.50 17.23 C ATOM 902 CB ASER A 100 2.651 −57.928 0.238 0.50 16.94 C ATOM 903 CB BSER A 100 2.535 −58.308 0.306 0.50 16.59 C ATOM 904 OG ASER A 100 1.577 −57.637 −0.624 0.50 14.44 O ATOM 905 OG BSER A 100 2.369 −57.063 −0.329 0.50 12.87 O ATOM 906 C SER A 100 3.524 −59.151 −1.834 1.00 17.22 C ATOM 907 O SER A 100 4.073 −58.318 −2.586 1.00 17.03 O ATOM 908 N ALA A 101 2.818 −60.190 −2.281 1.00 16.93 N ATOM 909 CA ALA A 101 2.537 −60.338 −3.706 1.00 17.51 C ATOM 910 CB ALA A 101 1.614 −61.491 −3.959 1.00 16.81 C ATOM 911 C ALA A 101 1.943 −59.037 −4.234 1.00 18.49 C ATOM 912 O ALA A 101 2.372 −58.526 −5.280 1.00 18.21 O ATOM 913 N GLN A 102 0.979 −58.472 −3.515 1.00 17.00 N ATOM 914 CA GLN A 102 0.317 −57.230 −3.992 1.00 18.27 C ATOM 915 CB GLN A 102 −0.888 −56.897 −3.103 1.00 17.88 C ATOM 916 CG GLN A 102 −1.859 −55.885 −3.700 1.00 19.53 C ATOM 917 CD GLN A 102 −1.444 −54.431 −3.510 1.00 23.04 C ATOM 918 OE1 GLN A 102 −0.656 −54.092 −2.616 1.00 23.83 O ATOM 919 NE2 GLN A 102 −1.993 −53.554 −4.353 1.00 28.57 N ATOM 920 C GLN A 102 1.251 −56.007 −4.142 1.00 17.78 C ATOM 921 O GLN A 102 1.079 −55.172 −5.050 1.00 17.61 O ATOM 922 N LEU A 103 2.226 −55.886 −3.254 1.00 18.32 N ATOM 923 CA LEU A 103 3.163 −54.764 −3.327 1.00 18.80 C ATOM 924 CB LEU A 103 3.917 −54.569 −1.994 1.00 19.13 C ATOM 925 CG LEU A 103 3.130 −54.030 −0.778 1.00 20.28 C ATOM 926 CD1 LEU A 103 4.002 −54.062 0.452 1.00 21.70 C ATOM 927 CD2 LEU A 103 2.522 −52.644 −0.962 1.00 20.12 C ATOM 928 C LEU A 103 4.153 −54.877 −4.508 1.00 18.54 C ATOM 929 O LEU A 103 4.830 −53.903 −4.832 1.00 19.62 O ATOM 930 N ARG A 104 4.231 −56.041 −5.149 1.00 17.51 N ATOM 931 CA ARG A 104 5.091 −56.176 −6.345 1.00 18.29 C ATOM 932 CB ARG A 104 5.338 −57.633 −6.721 1.00 16.19 C ATOM 933 CG ARG A 104 4.289 −58.190 −7.703 1.00 16.36 C ATOM 934 CD ARG A 104 4.403 −59.709 −7.817 1.00 18.46 C ATOM 935 NE ARG A 104 3.564 −60.300 −8.867 1.00 17.38 N ATOM 936 CZ ARG A 104 2.255 −60.495 −8.789 1.00 22.43 C ATOM 937 NH1 ARG A 104 1.620 −61.043 −9.802 1.00 21.31 N ATOM 938 NH2 ARG A 104 1.572 −60.145 −7.699 1.00 22.90 N ATOM 939 C ARG A 104 4.469 −55.453 −7.549 1.00 19.41 C ATOM 940 O ARG A 104 5.187 −55.104 −8.501 1.00 19.36 O ATOM 941 N LEU A 105 3.166 −55.174 −7.492 1.00 18.48 N ATOM 942 CA LEU A 105 2.430 −54.780 −8.716 1.00 18.92 C ATOM 943 CB LEU A 105 0.894 −55.010 −8.612 1.00 18.99 C ATOM 944 CG LEU A 105 0.383 −56.466 −8.488 1.00 20.55 C ATOM 945 CD1 LEU A 105 −1.127 −56.595 −7.931 1.00 19.75 C ATOM 946 CD2 LEU A 105 0.626 −57.244 −9.826 1.00 20.09 C ATOM 947 C LEU A 105 2.757 −53.386 −9.275 1.00 19.99 C ATOM 948 O LEU A 105 3.012 −53.267 −10.479 1.00 17.61 O ATOM 949 N ALA A 106 2.720 −52.339 −8.440 1.00 19.37 N ATOM 950 CA ALA A 106 3.105 −51.001 −8.960 1.00 20.85 C ATOM 951 CB ALA A 106 2.943 −49.860 −7.898 1.00 20.53 C ATOM 952 C ALA A 106 4.516 −50.985 −9.587 1.00 20.65 C ATOM 953 O ALA A 106 4.650 −50.533 −10.723 1.00 21.70 O ATOM 954 N PRO A 107 5.576 −51.428 −8.856 1.00 20.32 N ATOM 955 CA PRO A 107 6.868 −51.411 −9.562 1.00 20.33 C ATOM 956 CB PRO A 107 7.908 −51.757 −8.463 1.00 21.24 C ATOM 957 CG PRO A 107 7.078 −52.441 −7.373 1.00 21.13 C ATOM 958 CD PRO A 107 5.711 −51.828 −7.431 1.00 20.65 C ATOM 959 C PRO A 107 6.978 −52.377 −10.751 1.00 19.27 C ATOM 960 O PRO A 107 7.735 −52.069 −11.672 1.00 19.36 O ATOM 961 N LEU A 108 6.253 −53.494 −10.752 1.00 18.15 N ATOM 962 CA LEU A 108 6.191 −54.318 −11.939 1.00 18.98 C ATOM 963 CB LEU A 108 5.346 −55.580 −11.762 1.00 18.90 C ATOM 964 CG LEU A 108 5.147 −56.518 −12.971 1.00 18.87 C ATOM 965 CD1 LEU A 108 6.538 −57.138 −13.476 1.00 16.05 C ATOM 966 CD2 LEU A 108 4.151 −57.637 −12.549 1.00 18.53 C ATOM 967 C LEU A 108 5.708 −53.531 −13.158 1.00 19.14 C ATOM 968 O LEU A 108 6.321 −53.632 −14.231 1.00 19.08 O ATOM 969 N TYR A 109 4.631 −52.776 −13.001 1.00 19.18 N ATOM 970 CA TYR A 109 4.086 −51.963 −14.086 1.00 20.04 C ATOM 971 CB TYR A 109 2.753 −51.239 −13.692 1.00 21.52 C ATOM 972 CG TYR A 109 1.644 −52.092 −13.134 1.00 25.19 C ATOM 973 CD1 TYR A 109 1.370 −53.364 −13.646 1.00 25.04 C ATOM 974 CE1 TYR A 109 0.321 −54.135 −13.136 1.00 28.04 C ATOM 975 CZ TYR A 109 −0.479 −53.630 −12.128 1.00 25.98 C ATOM 976 OH TYR A 109 −1.497 −54.404 −11.622 1.00 30.37 O ATOM 977 CE2 TYR A 109 −0.271 −52.356 −11.615 1.00 26.89 C ATOM 978 CD2 TYR A 109 0.802 −51.589 −12.114 1.00 23.64 C ATOM 979 C TYR A 109 5.090 −50.903 −14.499 1.00 19.77 C ATOM 980 O TYR A 109 5.223 −50.618 −15.703 1.00 19.68 O ATOM 981 N ALA A 110 5.801 −50.302 −13.536 1.00 18.69 N ATOM 982 CA ALA A 110 6.864 −49.350 −13.917 1.00 18.23 C ATOM 983 CB ALA A 110 7.408 −48.650 −12.670 1.00 17.00 C ATOM 984 C ALA A 110 8.009 −50.006 −14.733 1.00 19.53 C ATOM 985 O ALA A 110 8.533 −49.404 −15.727 1.00 19.35 O ATOM 986 N SER A 111 8.394 −51.228 −14.358 1.00 18.40 N ATOM 987 CA SER A 111 9.478 −51.923 −15.049 1.00 19.16 C ATOM 988 CB SER A 111 9.909 −53.150 −14.234 1.00 18.49 C ATOM 989 OG SER A 111 9.017 −54.219 −14.473 1.00 21.25 O ATOM 990 C SER A 111 8.990 −52.274 −16.484 1.00 19.02 C ATOM 991 O SER A 111 9.772 −52.220 −17.446 1.00 19.51 O ATOM 992 N ALA A 112 7.717 −52.654 −16.629 1.00 19.25 N ATOM 993 CA ALA A 112 7.179 −52.979 −17.960 1.00 19.05 C ATOM 994 CB ALA A 112 5.777 −53.639 −17.893 1.00 20.36 C ATOM 995 C ALA A 112 7.122 −51.700 −18.836 1.00 19.81 C ATOM 996 O ALA A 112 7.477 −51.768 −20.021 1.00 19.05 O ATOM 997 N ARG A 113 6.673 −50.563 −18.287 1.00 17.74 N ATOM 998 CA ARG A 113 6.652 −49.353 −19.087 1.00 17.00 C ATOM 999 CB ARG A 113 6.061 −48.196 −18.298 1.00 17.26 C ATOM 1000 CG ARG A 113 4.568 −48.332 −18.063 1.00 16.75 C ATOM 1001 CD ARG A 113 3.935 −47.099 −17.409 1.00 19.58 C ATOM 1002 NE ARG A 113 4.479 −46.774 −16.091 1.00 22.43 N ATOM 1003 CZ ARG A 113 3.924 −47.134 −14.924 1.00 26.06 C ATOM 1004 NH1 ARG A 113 2.805 −47.874 −14.895 1.00 25.88 N ATOM 1005 NH2 ARG A 113 4.490 −46.752 −13.777 1.00 20.88 N ATOM 1006 C ARG A 113 8.118 −49.034 −19.561 1.00 17.10 C ATOM 1007 O ARG A 113 8.351 −48.662 −20.728 1.00 15.69 O ATOM 1008 N ALA A 114 9.104 −49.167 −18.656 1.00 16.30 N ATOM 1009 CA ALA A 114 10.484 −48.825 −19.025 1.00 17.08 C ATOM 1010 CB ALA A 114 11.411 −48.740 −17.775 1.00 16.19 C ATOM 1011 C ALA A 114 11.025 −49.835 −20.072 1.00 16.54 C ATOM 1012 O ALA A 114 11.700 −49.443 −21.067 1.00 16.39 O ATOM 1013 N LEU A 115 10.703 −51.114 −19.904 1.00 15.42 N ATOM 1014 CA LEU A 115 11.185 −52.091 −20.882 1.00 16.02 C ATOM 1015 CB LEU A 115 10.997 −53.512 −20.375 1.00 14.14 C ATOM 1016 CG LEU A 115 11.579 −54.643 −21.234 1.00 16.65 C ATOM 1017 CD1 LEU A 115 13.111 −54.447 −21.524 1.00 18.28 C ATOM 1018 CD2 LEU A 115 11.299 −55.970 −20.544 1.00 16.70 C ATOM 1019 C LEU A 115 10.522 −51.870 −22.268 1.00 16.10 C ATOM 1020 O LEU A 115 11.187 −51.971 −23.332 1.00 13.56 O ATOM 1021 N TRP A 116 9.215 −51.586 −22.266 1.00 15.42 N ATOM 1022 CA TRP A 116 8.561 −51.387 −23.532 1.00 16.32 C ATOM 1023 CB TRP A 116 7.023 −51.421 −23.390 1.00 17.44 C ATOM 1024 CG TRP A 116 6.522 −52.852 −23.299 1.00 21.79 C ATOM 1025 CD1 TRP A 116 6.052 −53.495 −22.178 1.00 26.43 C ATOM 1026 NE1 TRP A 116 5.682 −54.789 −22.487 1.00 26.72 N ATOM 1027 CE2 TRP A 116 5.942 −55.019 −23.816 1.00 27.72 C ATOM 1028 CD2 TRP A 116 6.474 −53.819 −24.362 1.00 24.70 C ATOM 1029 CE3 TRP A 116 6.818 −53.785 −25.726 1.00 25.83 C ATOM 1030 CZ3 TRP A 116 6.614 −54.934 −26.507 1.00 24.24 C ATOM 1031 CH2 TRP A 116 6.076 −56.123 −25.939 1.00 24.26 C ATOM 1032 CZ2 TRP A 116 5.730 −56.187 −24.606 1.00 25.52 C ATOM 1033 C TRP A 116 9.037 −50.107 −24.220 1.00 15.53 C ATOM 1034 O TRP A 116 9.086 −50.051 −25.449 1.00 14.21 O ATOM 1035 N LEU A 117 9.399 −49.089 −23.445 1.00 15.82 N ATOM 1036 CA LEU A 117 9.986 −47.877 −24.042 1.00 17.22 C ATOM 1037 CB LEU A 117 10.197 −46.796 −22.970 1.00 17.54 C ATOM 1038 CG LEU A 117 10.651 −45.398 −23.417 1.00 21.03 C ATOM 1039 CD1 LEU A 117 9.805 −44.830 −24.609 1.00 20.36 C ATOM 1040 CD2 LEU A 117 10.638 −44.437 −22.221 1.00 19.16 C ATOM 1041 C LEU A 117 11.328 −48.244 −24.712 1.00 17.27 C ATOM 1042 O LEU A 117 11.609 −47.797 −25.846 1.00 15.68 O ATOM 1043 N LEU A 118 12.142 −49.059 −24.041 1.00 16.55 N ATOM 1044 CA LEU A 118 13.392 −49.546 −24.663 1.00 17.55 C ATOM 1045 CB LEU A 118 14.273 −50.408 −23.731 1.00 18.46 C ATOM 1046 CG LEU A 118 15.191 −49.703 −22.756 1.00 21.32 C ATOM 1047 CD1 LEU A 118 15.748 −50.742 −21.729 1.00 19.72 C ATOM 1048 CD2 LEU A 118 16.305 −48.908 −23.516 1.00 16.31 C ATOM 1049 C LEU A 118 13.138 −50.336 −25.925 1.00 17.98 C ATOM 1050 O LEU A 118 13.866 −50.163 −26.874 1.00 17.15 O ATOM 1051 N VAL A 119 12.117 −51.209 −25.924 1.00 15.44 N ATOM 1052 CA VAL A 119 11.753 −51.942 −27.113 1.00 15.10 C ATOM 1053 CB VAL A 119 10.651 −52.958 −26.806 1.00 15.45 C ATOM 1054 CG1 VAL A 119 9.996 −53.488 −28.104 1.00 16.21 C ATOM 1055 CG2 VAL A 119 11.233 −54.153 −25.931 1.00 14.62 C ATOM 1056 C VAL A 119 11.370 −50.934 −28.255 1.00 15.50 C ATOM 1057 O VAL A 119 11.804 −51.079 −29.425 1.00 15.89 O ATOM 1058 N ALA A 120 10.595 −49.917 −27.920 1.00 14.80 N ATOM 1059 CA ALA A 120 10.122 −48.958 −28.923 1.00 15.99 C ATOM 1060 CB ALA A 120 9.072 −47.985 −28.303 1.00 14.80 C ATOM 1061 C ALA A 120 11.318 −48.179 −29.504 1.00 16.00 C ATOM 1062 O ALA A 120 11.379 −47.945 −30.720 1.00 16.41 O ATOM 1063 N LEU A 121 12.283 −47.816 −28.654 1.00 16.45 N ATOM 1064 CA LEU A 121 13.465 −47.091 −29.135 1.00 17.42 C ATOM 1065 CB LEU A 121 14.317 −46.544 −27.976 1.00 16.44 C ATOM 1066 CG LEU A 121 13.680 −45.572 −26.984 1.00 15.90 C ATOM 1067 CD1 LEU A 121 14.771 −44.996 −26.054 1.00 18.04 C ATOM 1068 CD2 LEU A 121 12.933 −44.435 −27.714 1.00 18.56 C ATOM 1069 C LEU A 121 14.324 −47.982 −30.022 1.00 17.33 C ATOM 1070 O LEU A 121 14.815 −47.523 −31.078 1.00 16.03 O ATOM 1071 N ALA A 122 14.514 −49.231 −29.597 1.00 16.06 N ATOM 1072 CA ALA A 122 15.196 −50.217 −30.436 1.00 16.34 C ATOM 1073 CB ALA A 122 15.286 −51.566 −29.722 1.00 14.36 C ATOM 1074 C ALA A 122 14.495 −50.351 −31.826 1.00 16.12 C ATOM 1075 O ALA A 122 15.183 −50.332 −32.849 1.00 17.12 O ATOM 1076 N ALA A 123 13.182 −50.506 −31.829 1.00 14.68 N ATOM 1077 CA ALA A 123 12.384 −50.662 −33.065 1.00 16.66 C ATOM 1078 CB ALA A 123 10.879 −50.939 −32.782 1.00 15.93 C ATOM 1079 C ALA A 123 12.513 −49.414 −33.952 1.00 16.24 C ATOM 1080 O ALA A 123 12.775 −49.555 −35.136 1.00 14.50 O ATOM 1081 N LEU A 124 12.434 −48.218 −33.350 1.00 16.22 N ATOM 1082 CA LEU A 124 12.528 −47.002 −34.144 1.00 16.16 C ATOM 1083 CB LEU A 124 12.214 −45.765 −33.268 1.00 16.21 C ATOM 1084 CG LEU A 124 10.745 −45.643 −32.820 1.00 18.15 C ATOM 1085 CD1 LEU A 124 10.578 −44.457 −31.794 1.00 20.40 C ATOM 1086 CD2 LEU A 124 9.857 −45.414 −34.070 1.00 19.87 C ATOM 1087 C LEU A 124 13.941 −46.862 −34.724 1.00 17.00 C ATOM 1088 O LEU A 124 14.077 −46.444 −35.850 1.00 17.42 O ATOM 1089 N GLY A 125 14.982 −47.169 −33.940 1.00 16.35 N ATOM 1090 CA GLY A 125 16.341 −47.076 −34.412 1.00 16.72 C ATOM 1091 C GLY A 125 16.601 −48.052 −35.568 1.00 16.98 C ATOM 1092 O GLY A 125 17.245 −47.704 −36.594 1.00 16.12 O ATOM 1093 N LEU A 126 16.099 −49.275 −35.434 1.00 15.83 N ATOM 1094 CA LEU A 126 16.178 −50.251 −36.556 1.00 15.68 C ATOM 1095 CB LEU A 126 15.763 −51.657 −36.095 1.00 14.31 C ATOM 1096 CG LEU A 126 16.811 −52.334 −35.153 1.00 12.27 C ATOM 1097 CD1 LEU A 126 16.224 −53.623 −34.530 1.00 12.70 C ATOM 1098 CD2 LEU A 126 18.123 −52.643 −35.856 1.00 14.00 C ATOM 1099 C LEU A 126 15.379 −49.819 −37.820 1.00 17.51 C ATOM 1100 O LEU A 126 15.847 −49.981 −38.942 1.00 16.62 O ATOM 1101 N LEU A 127 14.175 −49.296 −37.622 1.00 16.40 N ATOM 1102 CA LEU A 127 13.392 −48.803 −38.711 1.00 19.64 C ATOM 1103 CB LEU A 127 12.060 −48.301 −38.175 1.00 20.16 C ATOM 1104 CG LEU A 127 10.743 −48.841 −38.708 1.00 31.03 C ATOM 1105 CD1 LEU A 127 9.840 −49.172 −37.438 1.00 34.65 C ATOM 1106 CD2 LEU A 127 10.780 −50.067 −39.690 1.00 35.41 C ATOM 1107 C LEU A 127 14.166 −47.668 −39.451 1.00 18.74 C ATOM 1108 O LEU A 127 14.200 −47.671 −40.691 1.00 16.96 O ATOM 1109 N ALA A 128 14.796 −46.760 −38.687 1.00 18.28 N ATOM 1110 CA ALA A 128 15.575 −45.653 −39.225 1.00 20.21 C ATOM 1111 CB ALA A 128 16.082 −44.713 −38.128 1.00 18.89 C ATOM 1112 C ALA A 128 16.748 −46.184 −40.034 1.00 19.78 C ATOM 1113 O ALA A 128 17.078 −45.631 −41.090 1.00 19.15 O ATOM 1114 N HIS A 129 17.334 −47.281 −39.569 1.00 18.53 N ATOM 1115 CA HIS A 129 18.390 −47.936 −40.278 1.00 17.66 C ATOM 1116 CB HIS A 129 19.128 −48.951 −39.368 1.00 17.32 C ATOM 1117 CG HIS A 129 20.207 −49.688 −40.083 1.00 15.76 C ATOM 1118 ND1 HIS A 129 21.499 −49.207 −40.181 1.00 18.37 N ATOM 1119 CE1 HIS A 129 22.208 −50.012 −40.951 1.00 17.41 C ATOM 1120 NE2 HIS A 129 21.433 −51.011 −41.335 1.00 17.22 N ATOM 1121 CD2 HIS A 129 20.174 −50.830 −40.812 1.00 16.46 C ATOM 1122 C HIS A 129 17.959 −48.598 −41.615 1.00 18.81 C ATOM 1123 O HIS A 129 18.658 −48.456 −42.604 1.00 18.01 O ATOM 1124 N PHE A 130 16.883 −49.375 −41.618 1.00 16.57 N ATOM 1125 CA PHE A 130 16.515 −50.193 −42.766 1.00 17.26 C ATOM 1126 CB PHE A 130 15.903 −51.507 −42.328 1.00 16.04 C ATOM 1127 CG PHE A 130 16.898 −52.486 −41.755 1.00 16.37 C ATOM 1128 CD1 PHE A 130 17.796 −53.141 −42.603 1.00 16.48 C ATOM 1129 CE1 PHE A 130 18.698 −54.070 −42.097 1.00 17.18 C ATOM 1130 CZ PHE A 130 18.712 −54.361 −40.741 1.00 13.56 C ATOM 1131 CE2 PHE A 130 17.855 −53.709 −39.877 1.00 13.23 C ATOM 1132 CD2 PHE A 130 16.906 −52.788 −40.389 1.00 16.06 C ATOM 1133 C PHE A 130 15.513 −49.549 −43.767 1.00 18.83 C ATOM 1134 O PHE A 130 15.552 −49.888 −44.943 1.00 17.40 O ATOM 1135 N LEU A 131 14.608 −48.708 −43.275 1.00 18.27 N ATOM 1136 CA LEU A 131 13.485 −48.269 −44.080 1.00 21.82 C ATOM 1137 CB LEU A 131 12.370 −47.660 −43.205 1.00 21.96 C ATOM 1138 CG LEU A 131 11.015 −47.296 −43.820 1.00 26.12 C ATOM 1139 CD1 LEU A 131 10.370 −48.451 −44.570 1.00 24.52 C ATOM 1140 CD2 LEU A 131 10.118 −46.786 −42.672 1.00 25.75 C ATOM 1141 C LEU A 131 13.907 −47.372 −45.270 1.00 20.69 C ATOM 1142 O LEU A 131 13.422 −47.579 −46.363 1.00 19.41 O ATOM 1143 N PRO A 132 14.807 −46.397 −45.065 1.00 20.35 N ATOM 1144 CA PRO A 132 15.179 −45.565 −46.237 1.00 21.17 C ATOM 1145 CB PRO A 132 16.169 −44.527 −45.642 1.00 20.75 C ATOM 1146 CG PRO A 132 15.712 −44.417 −44.183 1.00 21.79 C ATOM 1147 CD PRO A 132 15.431 −45.898 −43.838 1.00 21.43 C ATOM 1148 C PRO A 132 15.787 −46.378 −47.393 1.00 21.10 C ATOM 1149 O PRO A 132 15.299 −46.253 −48.544 1.00 21.92 O ATOM 1150 N ALA A 133 16.818 −47.201 −47.138 1.00 19.00 N ATOM 1151 CA ALA A 133 17.344 −48.048 −48.217 1.00 18.47 C ATOM 1152 CB ALA A 133 18.518 −48.909 −47.744 1.00 17.70 C ATOM 1153 C ALA A 133 16.269 −48.954 −48.827 1.00 17.62 C ATOM 1154 O ALA A 133 16.280 −49.222 −50.033 1.00 17.85 O ATOM 1155 N ALA A 134 15.365 −49.477 −48.006 1.00 16.95 N ATOM 1156 CA ALA A 134 14.323 −50.370 −48.539 1.00 16.86 C ATOM 1157 CB ALA A 134 13.561 −51.110 −47.364 1.00 16.97 C ATOM 1158 C ALA A 134 13.333 −49.605 −49.454 1.00 16.39 C ATOM 1159 O ALA A 134 12.941 −50.098 −50.545 1.00 16.55 O ATOM 1160 N LEU A 135 12.933 −48.408 −49.034 1.00 15.20 N ATOM 1161 CA LEU A 135 12.029 −47.603 −49.846 1.00 15.77 C ATOM 1162 CB LEU A 135 11.573 −46.361 −49.084 1.00 16.04 C ATOM 1163 CG LEU A 135 10.594 −46.641 −47.903 1.00 19.35 C ATOM 1164 CD1 LEU A 135 10.386 −45.419 −46.960 1.00 18.88 C ATOM 1165 CD2 LEU A 135 9.207 −47.183 −48.417 1.00 22.05 C ATOM 1166 C LEU A 135 12.709 −47.210 −51.162 1.00 16.61 C ATOM 1167 O LEU A 135 12.070 −47.243 −52.241 1.00 16.10 O ATOM 1168 N ARG A 136 13.991 −46.804 −51.075 1.00 15.57 N ATOM 1169 CA ARG A 136 14.763 −46.510 −52.269 1.00 16.20 C ATOM 1170 CB ARG A 136 16.161 −46.028 −51.936 1.00 15.74 C ATOM 1171 CG ARG A 136 16.849 −45.714 −53.265 1.00 20.45 C ATOM 1172 CD ARG A 136 18.125 −45.020 −53.101 1.00 23.94 C ATOM 1173 NE ARG A 136 19.055 −45.805 −52.341 1.00 24.94 N ATOM 1174 CZ ARG A 136 20.337 −45.497 −52.189 1.00 33.93 C ATOM 1175 NH1 ARG A 136 20.852 −44.420 −52.788 1.00 30.17 N ATOM 1176 NH2 ARG A 136 21.112 −46.263 −51.406 1.00 36.07 N ATOM 1177 C ARG A 136 14.862 −47.649 −53.268 1.00 16.02 C ATOM 1178 O ARG A 136 14.647 −47.428 −54.447 1.00 16.39 O ATOM 1179 N ALA A 137 15.139 −48.875 −52.795 1.00 16.10 N ATOM 1180 CA ALA A 137 15.273 −50.026 −53.676 1.00 17.40 C ATOM 1181 CB ALA A 137 15.646 −51.280 −52.866 1.00 17.86 C ATOM 1182 C ALA A 137 13.966 −50.271 −54.414 1.00 17.27 C ATOM 1183 O ALA A 137 13.955 −50.569 −55.602 1.00 19.04 O ATOM 1184 N ALA A 138 12.874 −50.115 −53.692 1.00 17.64 N ATOM 1185 CA ALA A 138 11.538 −50.310 −54.227 1.00 18.93 C ATOM 1186 CB ALA A 138 10.521 −50.282 −53.087 1.00 17.91 C ATOM 1187 C ALA A 138 11.184 −49.267 −55.271 1.00 18.76 C ATOM 1188 O ALA A 138 10.620 −49.579 −56.337 1.00 18.73 O ATOM 1189 N LEU A 139 11.487 −48.015 −54.963 1.00 19.53 N ATOM 1190 CA LEU A 139 11.342 −46.931 −55.938 1.00 20.25 C ATOM 1191 CB LEU A 139 11.686 −45.590 −55.301 1.00 21.38 C ATOM 1192 CG LEU A 139 10.641 −45.145 −54.268 1.00 25.15 C ATOM 1193 CD1 LEU A 139 11.216 −44.148 −53.214 1.00 28.08 C ATOM 1194 CD2 LEU A 139 9.405 −44.534 −55.026 1.00 30.13 C ATOM 1195 C LEU A 139 12.173 −47.132 −57.186 1.00 20.70 C ATOM 1196 O LEU A 139 11.669 −46.939 −58.309 1.00 20.05 O ATOM 1197 N LEU A 140 13.437 −47.507 −57.015 1.00 21.05 N ATOM 1198 CA LEU A 140 14.324 −47.812 −58.147 1.00 21.95 C ATOM 1199 CB LEU A 140 15.742 −48.164 −57.659 1.00 20.37 C ATOM 1200 CG LEU A 140 16.573 −47.022 −57.030 1.00 21.37 C ATOM 1201 CD1 LEU A 140 17.914 −47.544 −56.486 1.00 19.31 C ATOM 1202 CD2 LEU A 140 16.833 −45.831 −57.959 1.00 18.14 C ATOM 1203 C LEU A 140 13.763 −48.910 −59.082 1.00 24.36 C ATOM 1204 O LEU A 140 13.821 −48.756 −60.316 1.00 25.16 O ATOM 1205 N GLY A 141 13.186 −49.966 −58.502 1.00 26.81 N ATOM 1206 CA GLY A 141 12.579 −51.064 −59.253 1.00 31.10 C ATOM 1207 C GLY A 141 11.416 −50.610 −60.122 1.00 34.70 C ATOM 1208 O GLY A 141 11.243 −51.084 −61.225 1.00 32.81 O ATOM 1209 N ARG A 142 10.618 −49.699 −59.590 1.00 39.98 N ATOM 1210 CA ARG A 142 9.636 −48.912 −60.339 1.00 47.21 C ATOM 1211 CB ARG A 142 8.992 −47.999 −59.301 1.00 46.48 C ATOM 1212 CG ARG A 142 7.530 −47.769 −59.365 1.00 47.57 C ATOM 1213 CD ARG A 142 6.880 −48.470 −58.163 1.00 49.36 C ATOM 1214 NE ARG A 142 7.334 −49.859 −58.068 1.00 48.64 N ATOM 1215 CZ ARG A 142 7.128 −50.786 −59.006 1.00 46.60 C ATOM 1216 NH1 ARG A 142 7.592 −52.021 −58.821 1.00 45.63 N ATOM 1217 NH2 ARG A 142 6.478 −50.476 −60.127 1.00 44.87 N ATOM 1218 C ARG A 142 10.209 −47.987 −61.453 1.00 52.70 C ATOM 1219 O ARG A 142 9.432 −47.576 −62.295 1.00 52.86 O ATOM 1220 N LEU A 143 11.525 −47.593 −61.427 1.00 62.69 N ATOM 1221 CA LEU A 143 11.920 −46.384 −62.212 1.00 64.17 C ATOM 1222 CB LEU A 143 13.239 −45.745 −61.870 1.00 65.77 C ATOM 1223 CG LEU A 143 13.363 −44.199 −62.043 1.00 66.48 C ATOM 1224 CD1 LEU A 143 14.866 −43.842 −62.267 1.00 64.58 C ATOM 1225 CD2 LEU A 143 12.594 −43.410 −60.921 1.00 67.46 C ATOM 1226 C LEU A 143 11.538 −46.348 −63.776 1.00 64.64 C ATOM 1227 O LEU A 143 10.895 −45.373 −64.173 1.00 63.76 O ATOM 1228 N ARG A 144 11.711 −47.340 −64.674 1.00 65.81 N ATOM 1229 CA ARG A 144 11.472 −48.800 −64.608 1.00 67.60 C ATOM 1230 CB ARG A 144 12.270 −49.486 −63.489 1.00 67.22 C ATOM 1231 CG ARG A 144 13.611 −50.012 −63.961 1.00 67.14 C ATOM 1232 CD ARG A 144 14.762 −49.098 −63.576 1.00 66.63 C ATOM 1233 NE ARG A 144 15.617 −49.646 −62.511 1.00 66.32 N ATOM 1234 CZ ARG A 144 16.045 −50.908 −62.426 1.00 65.42 C ATOM 1235 NH1 ARG A 144 15.727 −51.797 −63.358 1.00 65.86 N ATOM 1236 NH2 ARG A 144 16.814 −51.284 −61.406 1.00 64.70 N ATOM 1237 C ARG A 144 9.976 −49.283 −64.765 1.00 68.80 C ATOM 1238 O ARG A 144 9.690 −50.525 −64.722 1.00 70.00 O ATOM 1239 N THR A 145 9.034 −48.412 −65.177 1.00 69.68 N ATOM 1240 CA THR A 145 9.096 −47.477 −66.337 1.00 69.98 C ATOM 1241 CB THR A 145 8.231 −46.175 −66.181 1.00 70.25 C ATOM 1242 OG1 THR A 145 8.896 −45.301 −65.144 1.00 66.72 O ATOM 1243 CG2 THR A 145 6.614 −46.590 −65.622 1.00 72.03 C ATOM 1244 C THR A 145 10.431 −47.269 −67.053 1.00 69.95 C ATOM 1245 O THR A 145 11.307 −48.148 −67.025 1.00 70.10 O ATOM 1246 N GLY A 146 10.558 −46.129 −67.737 1.00 69.96 N ATOM 1247 CA GLY A 146 11.813 −45.762 −68.406 1.00 69.80 C ATOM 1248 C GLY A 146 12.044 −46.547 −69.680 1.00 69.62 C ATOM 1249 O GLY A 146 11.374 −47.551 −69.941 1.00 69.65 O ATOM 1250 N GLY A 147 13.010 −46.095 −70.472 1.00 69.53 N ATOM 1251 CA GLY A 147 13.159 −46.584 −71.841 1.00 69.36 C ATOM 1252 C GLY A 147 12.007 −46.020 −72.654 1.00 69.18 C ATOM 1253 O GLY A 147 11.626 −46.574 −73.694 1.00 69.16 O ATOM 1254 N GLY A 148 11.456 −44.913 −72.149 1.00 69.04 N ATOM 1255 CA GLY A 148 10.290 −44.249 −72.722 1.00 68.96 C ATOM 1256 C GLY A 148 9.878 −43.109 −71.809 1.00 68.92 C ATOM 1257 O GLY A 148 10.465 −42.027 −71.867 1.00 68.87 O ATOM 1258 N ALA A 149 8.866 −43.372 −70.973 1.00 68.88 N ATOM 1259 CA ALA A 149 8.372 −42.473 −69.898 1.00 68.77 C ATOM 1260 CB ALA A 149 9.305 −42.526 −68.667 1.00 68.75 C ATOM 1261 C ALA A 149 7.990 −41.014 −70.252 1.00 68.67 C ATOM 1262 O ALA A 149 8.352 −40.418 −71.288 1.00 68.52 O ATOM 1263 OXT ALA A 149 7.277 −40.367 −69.463 1.00 68.63 O ATOM 1264 NI NI B 1 36.095 −48.980 −36.056 0.33 33.22 NI ATOM 1265 NI NI B 2 49.606 −49.606 −35.233 0.30 36.96 NI ATOM 1266 NI NI B 3 42.873 −48.586 −37.142 1.00 99.29 NI ATOM 1267 O6′ LMT C 1 −3.605 −54.087 −16.040 1.00 111.04 O ATOM 1268 C6′ LMT C 1 −3.173 −52.979 −16.843 1.00 111.18 C ATOM 1269 C5′ LMT C 1 −1.887 −52.371 −16.274 1.00 110.81 C ATOM 1270 C4′ LMT C 1 −2.229 −51.126 −15.451 1.00 111.06 C ATOM 1271 C3′ LMT C 1 −1.040 −50.157 −15.294 1.00 110.38 C ATOM 1272 O3′ LMT C 1 −1.525 −48.852 −14.957 1.00 110.45 O ATOM 1273 C2′ LMT C 1 −0.198 −50.035 −16.572 1.00 109.55 C ATOM 1274 O2′ LMT C 1 0.917 −49.129 −16.433 1.00 108.76 O ATOM 1275 O1* LMT C 1 −2.731 −51.685 −14.228 1.00 112.51 O ATOM 1276 C1* LMT C 1 −3.206 −50.871 −13.139 1.00 114.57 C ATOM 1277 O5* LMT C 1 −3.559 −49.507 −13.446 1.00 115.19 O ATOM 1278 C5* LMT C 1 −3.688 −48.684 −12.266 1.00 116.27 C ATOM 1279 C6* LMT C 1 −2.468 −47.764 −12.142 1.00 116.61 C ATOM 1280 O6* LMT C 1 −2.877 −46.401 −11.930 1.00 117.41 O ATOM 1281 C4* LMT C 1 −3.875 −49.535 −10.989 1.00 116.40 C ATOM 1282 O4* LMT C 1 −4.351 −48.741 −9.886 1.00 116.75 O ATOM 1283 C3* LMT C 1 −4.784 −50.759 −11.194 1.00 115.88 C ATOM 1284 O3* LMT C 1 −4.708 −51.608 −10.038 1.00 116.21 O ATOM 1285 C2* LMT C 1 −4.383 −51.559 −12.435 1.00 115.09 C ATOM 1286 O2* LMT C 1 −5.498 −51.680 −13.327 1.00 115.04 O ATOM 1287 O5′ LMT C 1 −0.953 −52.135 −17.348 1.00 110.41 O ATOM 1288 C1′ LMT C 1 0.250 −51.426 −17.017 1.00 108.78 C ATOM 1289 O1′ LMT C 1 1.106 −51.303 −18.164 1.00 106.47 O ATOM 1290 C1 LMT C 1 2.109 −52.311 −18.332 1.00 102.89 C ATOM 1291 C2 LMT C 1 2.537 −52.390 −19.803 1.00 100.07 C ATOM 1292 C3 LMT C 1 2.902 −51.031 −20.400 1.00 98.03 C ATOM 1293 C4 LMT C 1 3.459 −51.122 −21.819 1.00 96.60 C ATOM 1294 C5 LMT C 1 2.360 −51.137 −22.884 1.00 96.20 C ATOM 1295 C6 LMT C 1 2.922 −51.294 −24.299 1.00 95.35 C ATOM 1296 C7 LMT C 1 1.961 −50.786 −25.367 1.00 93.83 C ATOM 1302 O6′ LMT C 2 −2.031 −55.756 −17.808 1.00 80.58 O ATOM 1303 C6′ LMT C 2 −0.935 −55.782 −16.876 1.00 81.63 C ATOM 1304 C5′ LMT C 2 0.251 −56.588 −17.425 1.00 81.73 C ATOM 1305 C4′ LMT C 2 1.210 −57.054 −16.314 1.00 80.51 C ATOM 1306 C3′ LMT C 2 2.449 −57.718 −16.932 1.00 80.88 C ATOM 1307 O3′ LMT C 2 3.394 −58.131 −15.930 1.00 79.99 O ATOM 1308 C2′ LMT C 2 3.110 −56.879 −18.031 1.00 81.76 C ATOM 1309 O2′ LMT C 2 4.179 −57.638 −18.607 1.00 79.74 O ATOM 1310 O1* LMT C 2 0.544 −58.048 −15.535 1.00 78.22 O ATOM 1311 C1* LMT C 2 0.619 −57.870 −14.117 1.00 76.69 C ATOM 1312 O5* LMT C 2 −0.584 −57.225 −13.653 1.00 77.46 O ATOM 1313 C5* LMT C 2 −1.784 −58.030 −13.671 1.00 77.02 C ATOM 1314 C6* LMT C 2 −2.979 −57.176 −13.253 1.00 76.34 C ATOM 1315 O6* LMT C 2 −2.670 −56.552 −12.006 1.00 73.92 O ATOM 1316 C4* LMT C 2 −1.561 −59.263 −12.785 1.00 76.97 C ATOM 1317 O4* LMT C 2 −2.735 −60.071 −12.643 1.00 78.21 O ATOM 1318 C3* LMT C 2 −0.438 −60.065 −13.427 1.00 75.75 C ATOM 1319 O3* LMT C 2 −0.293 −61.311 −12.744 1.00 76.68 O ATOM 1320 C2* LMT C 2 0.844 −59.217 −13.410 1.00 75.44 C ATOM 1321 O2* LMT C 2 1.963 −59.916 −13.988 1.00 70.89 O ATOM 1322 O5′ LMT C 2 0.957 −55.816 −18.416 1.00 83.00 O ATOM 1323 C1′ LMT C 2 2.039 −56.516 −19.082 1.00 83.33 C ATOM 1324 O1′ LMT C 2 2.579 −55.760 −20.194 1.00 84.31 O ATOM 1325 C1 LMT C 2 1.663 −55.598 −21.289 1.00 85.13 C ATOM 1326 C2 LMT C 2 2.370 −55.721 −22.634 1.00 85.59 C ATOM 1327 C3 LMT C 2 1.395 −55.459 −23.782 1.00 86.75 C ATOM 1328 C4 LMT C 2 2.041 −55.667 −25.155 1.00 87.26 C ATOM 1329 C5 LMT C 2 2.231 −54.342 −25.894 1.00 87.53 C ATOM 1330 C6 LMT C 2 3.114 −54.507 −27.130 1.00 88.69 C ATOM 1331 C7 LMT C 2 2.602 −53.707 −28.327 1.00 89.75 C ATOM 1332 C8 LMT C 2 3.551 −53.780 −29.524 1.00 90.13 C ATOM 1333 C9 LMT C 2 3.066 −54.744 −30.606 1.00 90.48 C ATOM 1334 C10 LMT C 2 4.237 −55.559 −31.157 1.00 91.10 C ATOM 1335 C11 LMT C 2 3.783 −56.629 −32.150 1.00 91.45 C ATOM 1336 C12 LMT C 2 4.278 −56.320 −33.547 1.00 91.61 C ATOM 1349 C11 ACD D 1 12.505 −43.590 −40.585 1.00 54.69 C ATOM 1350 C12 ACD D 1 12.648 −43.056 −39.353 1.00 54.82 C ATOM 1351 C13 ACD D 1 11.694 −43.364 −38.211 1.00 50.69 C ATOM 1352 C14 ACD D 1 12.041 −42.637 −36.904 1.00 49.48 C ATOM 1353 C15 ACD D 1 13.312 −42.542 −36.529 1.00 47.66 C ATOM 1354 C16 ACD D 1 13.824 −41.869 −35.272 1.00 47.27 C ATOM 1355 C17 ACD D 1 15.059 −42.648 −34.847 1.00 41.50 C ATOM 1356 C18 ACD D 1 16.371 −41.947 −35.187 1.00 43.04 C ATOM 1357 C19 ACD D 1 17.554 −42.814 −34.886 1.00 39.17 C ATOM 1358 C20 ACD D 1 18.724 −42.571 −35.826 1.00 42.68 C ATOM 1362 C2 PLM E 1 20.760 −40.781 −11.317 1.00 74.16 C ATOM 1363 C3 PLM E 1 21.878 −41.789 −11.595 1.00 74.65 C ATOM 1364 C4 PLM E 1 22.104 −42.705 −10.387 1.00 74.01 C ATOM 1365 C5 PLM E 1 23.002 −43.919 −10.663 1.00 72.47 C ATOM 1366 C6 PLM E 1 22.740 −45.015 −9.621 1.00 71.56 C ATOM 1367 C7 PLM E 1 23.972 −45.825 −9.214 1.00 70.48 C ATOM 1378 C1 PLM E 2 9.374 −55.594 −40.579 1.00 71.72 C ATOM 1380 C2 PLM E 2 10.009 −56.966 −40.680 1.00 72.26 C ATOM 1381 C3 PLM E 2 9.761 −57.587 −42.054 1.00 73.03 C ATOM 1382 C4 PLM E 2 11.014 −57.512 −42.926 1.00 74.51 C ATOM 1383 C5 PLM E 2 11.788 −58.832 −43.027 1.00 75.54 C ATOM 1384 C6 PLM E 2 12.096 −59.186 −44.489 1.00 75.76 C ATOM 1385 C7 PLM E 2 13.499 −59.769 −44.661 1.00 75.86 C ATOM 1386 C8 PLM E 2 13.586 −60.801 −45.788 1.00 76.18 C ATOM 1387 C9 PLM E 2 14.405 −60.291 −46.976 1.00 74.91 C ATOM 1396 C1 PLM E 3 13.409 −59.091 −38.243 1.00 43.40 C ATOM 1398 C2 PLM E 3 13.872 −59.588 −39.613 1.00 47.64 C ATOM 1399 C3 PLM E 3 15.354 −59.947 −39.674 1.00 45.49 C ATOM 1400 C4 PLM E 3 15.691 −60.300 −41.115 1.00 44.84 C ATOM 1401 C5 PLM E 3 17.055 −60.944 −41.231 1.00 45.47 C ATOM 1402 C6 PLM E 3 17.125 −61.793 −42.488 1.00 45.61 C ATOM 1403 C7 PLM E 3 18.434 −61.525 −43.213 1.00 50.54 C ATOM 1404 C8 PLM E 3 18.567 −62.151 −44.598 1.00 50.19 C ATOM 1405 C9 PLM E 3 19.881 −62.927 −44.668 1.00 51.53 C ATOM 1406 C10 PLM E 3 20.304 −63.298 −46.092 1.00 54.50 C ATOM 1414 C1 PLM E 4 11.495 −55.573 −46.829 1.00 60.10 C ATOM 1416 C2 PLM E 4 12.312 −54.868 −45.758 1.00 60.16 C ATOM 1417 C3 PLM E 4 11.480 −53.831 −44.993 1.00 58.00 C ATOM 1418 C4 PLM E 4 12.404 −53.062 −44.045 1.00 57.41 C ATOM 1419 C5 PLM E 4 11.701 −52.049 −43.146 1.00 55.27 C ATOM 1432 C1 PLM E 5 23.241 −52.587 −6.604 1.00 64.05 C ATOM 1434 C2 PLM E 5 22.971 −53.290 −5.290 1.00 65.83 C ATOM 1435 C3 PLM E 5 21.603 −52.879 −4.748 1.00 66.72 C ATOM 1436 C4 PLM E 5 21.522 −52.787 −3.227 1.00 66.62 C ATOM 1437 C5 PLM E 5 20.079 −52.504 −2.830 1.00 67.23 C ATOM 1438 C6 PLM E 5 19.977 −51.825 −1.479 1.00 68.89 C ATOM 1439 C7 PLM E 5 18.520 −51.679 −1.062 1.00 70.98 C ATOM 1440 C8 PLM E 5 18.079 −50.209 −1.116 1.00 72.90 C ATOM 1441 C9 PLM E 5 16.809 −49.942 −0.304 1.00 72.41 C ATOM 1442 C10 PLM E 5 16.133 −48.629 −0.701 1.00 74.15 C ATOM 1443 C11 PLM E 5 15.343 −48.738 −2.009 1.00 74.42 C ATOM 1444 C12 PLM E 5 14.304 −47.628 −2.145 1.00 75.37 C ATOM 1445 C13 PLM E 5 13.225 −48.052 −3.137 1.00 75.74 C ATOM 1446 C14 PLM E 5 11.990 −47.156 −3.065 1.00 75.82 C ATOM 1450 C1 PLM E 6 20.482 −51.252 −45.234 1.00 57.66 C ATOM 1452 C2 PLM E 6 19.557 −52.371 −45.650 1.00 60.20 C ATOM 1453 C3 PLM E 6 20.274 −53.611 −46.205 1.00 64.91 C ATOM 1454 C4 PLM E 6 20.408 −54.765 −45.201 1.00 66.16 C ATOM 1455 C5 PLM E 6 21.817 −55.381 −45.206 1.00 68.53 C ATOM 1456 C6 PLM E 6 21.905 −56.912 −45.227 1.00 68.79 C ATOM 1457 C7 PLM E 6 21.712 −57.577 −46.596 1.00 70.69 C ATOM 1458 C8 PLM E 6 20.949 −58.908 −46.519 1.00 70.78 C ATOM 1459 C9 PLM E 6 20.505 −59.466 −47.876 1.00 71.83 C ATOM 1468 C1 PLM E 7 18.225 −45.029 −10.107 1.00 74.92 C ATOM 1470 C2 PLM E 7 19.181 −46.059 −9.549 1.00 75.43 C ATOM 1471 C3 PLM E 7 18.786 −47.453 −10.029 1.00 76.14 C ATOM 1472 C4 PLM E 7 19.832 −48.520 −9.706 1.00 76.87 C ATOM 1473 C5 PLM E 7 19.375 −49.504 −8.633 1.00 76.41 C ATOM 1474 C6 PLM E 7 20.305 −49.510 −7.413 1.00 77.88 C ATOM 1475 C7 PLM E 7 20.259 −48.203 −6.604 1.00 78.46 C ATOM 1476 C8 PLM E 7 20.055 −48.371 −5.094 1.00 77.69 C ATOM 1477 C9 PLM E 7 18.984 −47.397 −4.584 1.00 78.07 C ATOM 1486 C1 PLM E 8 18.445 −56.498 −47.334 1.00 62.14 C ATOM 1488 C2 PLM E 8 17.684 −57.340 −46.328 1.00 60.03 C ATOM 1489 C3 PLM E 8 17.050 −56.385 −45.330 1.00 57.68 C ATOM 1490 C4 PLM E 8 16.340 −57.092 −44.184 1.00 54.58 C ATOM 1491 C5 PLM E 8 15.228 −56.195 −43.633 1.00 54.88 C ATOM 1492 C6 PLM E 8 15.387 −56.057 −42.120 1.00 52.46 C ATOM 1493 C7 PLM E 8 14.116 −55.964 −41.306 1.00 51.86 C ATOM 1494 C8 PLM E 8 14.015 −54.610 −40.626 1.00 51.66 C ATOM 1495 C9 PLM E 8 13.654 −54.634 −39.146 1.00 54.74 C ATOM 1496 C10 PLM E 8 12.638 −53.542 −38.802 1.00 56.92 C ATOM 1497 C11 PLM E 8 12.602 −53.118 −37.326 1.00 60.52 C ATOM 1498 C12 PLM E 8 11.662 −53.898 −36.395 1.00 61.15 C ATOM 1499 C13 PLM E 8 12.396 −55.029 −35.639 1.00 63.48 C ATOM 1500 C14 PLM E 8 11.653 −56.371 −35.496 1.00 61.80 C ATOM 1507 C3 PLM E 9 −3.388 −49.728 −1.656 1.00 77.81 C ATOM 1508 C4 PLM E 9 −3.796 −49.452 −3.103 1.00 77.86 C ATOM 1509 C5 PLM E 9 −2.831 −50.073 −4.115 1.00 77.90 C ATOM 1510 C6 PLM E 9 −3.415 −50.033 −5.526 1.00 77.11 C ATOM 1522 C1 PLM E 10 7.838 −53.489 −32.633 1.00 66.07 C ATOM 1524 C2 PLM E 10 6.779 −52.797 −31.806 1.00 66.68 C ATOM 1525 C3 PLM E 10 7.412 −52.127 −30.594 1.00 66.75 C ATOM 1526 C4 PLM E 10 6.522 −50.998 −30.056 1.00 67.37 C ATOM 1527 C5 PLM E 10 6.098 −51.170 −28.596 1.00 65.79 C ATOM 1528 C6 PLM E 10 5.278 −49.972 −28.109 1.00 65.57 C ATOM 1529 C7 PLM E 10 5.403 −49.732 −26.605 1.00 64.10 C ATOM 1530 C8 PLM E 10 5.017 −48.304 −26.179 1.00 64.01 C ATOM 1531 C9 PLM E 10 6.061 −47.628 −25.289 1.00 60.09 C ATOM 1532 C10 PLM E 10 5.576 −47.317 −23.876 1.00 60.70 C ATOM 1543 C3 PLM E 11 17.260 −46.767 −62.233 1.00 77.12 C ATOM 1544 C4 PLM E 11 18.724 −47.213 −62.167 1.00 77.11 C ATOM 1545 C5 PLM E 11 18.843 −48.711 −61.868 1.00 76.32 C ATOM 1546 C6 PLM E 11 19.190 −49.036 −60.407 1.00 74.86 C ATOM 1547 C7 PLM E 11 20.474 −49.859 −60.243 1.00 72.18 C ATOM 1548 C8 PLM E 11 21.720 −49.012 −59.917 1.00 69.63 C ATOM 1549 C9 PLM E 11 22.043 −47.969 −60.999 1.00 66.36 C ATOM 1550 C10 PLM E 11 23.529 −47.634 −61.123 1.00 60.96 C ATOM 1551 C11 PLM E 11 23.744 −46.131 −60.959 1.00 53.56 C ATOM 1552 C12 PLM E 11 24.390 −45.814 −59.592 1.00 51.09 C ATOM 1553 C13 PLM E 11 24.083 −44.426 −59.014 1.00 35.34 C ATOM 1554 C14 PLM E 11 24.712 −44.175 −57.646 1.00 45.65 C ATOM 1555 C15 PLM E 11 23.750 −43.713 −56.535 1.00 41.07 C ATOM 1556 C16 PLM E 11 24.270 −42.627 −55.639 1.00 32.17 C ATOM 1557 O2 PLM E 12 26.718 −44.330 −29.929 1.00 63.05 O ATOM 1558 C1 PLM E 12 26.490 −45.566 −30.045 1.00 58.42 C ATOM 1559 O1 PLM E 12 26.039 −46.107 −29.007 1.00 50.98 O ATOM 1560 C2 PLM E 12 26.737 −46.349 −31.356 1.00 53.64 C ATOM 1561 C3 PLM E 12 28.168 −46.863 −31.443 1.00 52.96 C ATOM 1562 C4 PLM E 12 28.421 −48.250 −32.051 1.00 54.56 C ATOM 1563 C5 PLM E 12 29.529 −49.030 −31.332 1.00 54.51 C ATOM 1564 C6 PLM E 12 29.975 −50.290 −32.098 1.00 57.32 C ATOM 1565 C7 PLM E 12 29.451 −51.569 −31.440 1.00 55.35 C ATOM 1566 C8 PLM E 12 28.761 −52.503 −32.438 1.00 57.24 C ATOM 1567 C9 PLM E 12 28.307 −53.855 −31.866 1.00 53.71 C ATOM 1568 C10 PLM E 12 27.896 −53.890 −30.387 1.00 55.00 C ATOM 1569 C11 PLM E 12 26.788 −54.929 −30.188 1.00 52.46 C ATOM 1570 C12 PLM E 12 26.524 −55.352 −28.761 1.00 51.60 C ATOM 1571 C13 PLM E 12 25.142 −55.976 −28.756 1.00 49.17 C ATOM 1572 C14 PLM E 12 24.950 −57.102 −27.764 1.00 49.70 C ATOM 1573 C15 PLM E 12 23.480 −57.546 −27.752 1.00 50.03 C ATOM 1574 C16 PLM E 12 23.218 −58.681 −26.752 1.00 50.32 C ATOM 1583 C7 PLM E 13 22.537 −35.853 −28.273 1.00 81.67 C ATOM 1584 C8 PLM E 13 22.546 −36.528 −29.642 1.00 83.70 C ATOM 1585 C9 PLM E 13 23.842 −37.316 −29.873 1.00 84.89 C ATOM 1586 C10 PLM E 13 23.607 −38.545 −30.753 1.00 85.74 C ATOM 1587 C11 PLM E 13 24.896 −39.126 −31.341 1.00 87.42 C ATOM 1588 C12 PLM E 13 24.627 −40.414 −32.117 1.00 87.87 C ATOM 1589 C13 PLM E 13 25.824 −40.848 −32.964 1.00 88.32 C ATOM 1590 C14 PLM E 13 25.502 −42.108 −33.768 1.00 88.31 C ATOM 1591 C15 PLM E 13 26.127 −43.352 −33.133 1.00 88.25 C ATOM 1592 C16 PLM E 13 26.062 −44.553 −34.073 1.00 88.09 C ATOM 1593 S SO4 F 1 0.371 −60.843 0.415 0.50 33.47 S ATOM 1594 O1 SO4 F 1 0.768 −60.079 1.619 0.50 27.24 O ATOM 1595 O2 SO4 F 1 0.045 −59.903 −0.677 0.50 34.07 O ATOM 1596 O3 SO4 F 1 1.523 −61.656 −0.012 0.50 31.62 O ATOM 1597 O4 SO4 F 1 −0.770 −61.686 0.706 0.50 31.33 O ATOM 1598 S SO4 F 2 4.740 −61.413 −12.145 0.70 35.78 S ATOM 1599 O1 SO4 F 2 5.350 −60.844 −13.352 0.70 36.38 O ATOM 1600 O2 SO4 F 2 3.349 −61.045 −12.328 0.70 37.26 O ATOM 1601 O3 SO4 F 2 4.899 −62.845 −12.206 0.70 35.60 O ATOM 1602 O4 SO4 F 2 5.375 −61.026 −10.910 0.70 25.11 O ATOM 1603 O HOH G 1 15.375 −58.000 −15.073 1.00 22.82 O ATOM 1604 O HOH G 2 19.531 −46.287 −36.566 1.00 27.78 O ATOM 1605 O HOH G 3 29.517 −43.658 −23.829 1.00 30.07 O ATOM 1606 O HOH G 4 −0.278 −64.451 −2.346 1.00 70.05 O ATOM 1607 O HOH G 5 9.052 −51.779 −3.324 1.00 38.80 O ATOM 1608 O HOH G 6 16.885 −52.027 −46.008 1.00 36.95 O ATOM 1609 O HOH G 7 3.471 −48.240 −11.420 1.00 40.77 O ATOM 1610 O HOH G 8 20.174 −63.744 −13.015 1.00 38.14 O ATOM 1611 O HOH G 9 2.276 −60.434 2.999 1.00 39.02 O ATOM 1612 O HOH G 10 −0.002 −55.693 0.000 0.50 40.02 O ATOM 1613 O HOH G 11 5.511 −58.682 4.679 1.00 51.03 O ATOM 1614 O HOH G 12 9.721 −52.208 −56.796 1.00 56.88 O ATOM 1615 O HOH G 13 18.599 −48.824 −51.587 1.00 45.31 O ATOM 1616 O HOH G 14 14.316 −60.310 0.899 1.00 51.21 O ATOM 1617 O HOH G 15 12.024 −46.710 −11.705 1.00 39.84 O ATOM 1618 O HOH G 16 19.768 −63.332 −9.672 1.00 34.13 O ATOM 1619 O HOH G 17 11.715 −77.776 −5.495 1.00 60.38 O ATOM 1620 O HOH G 18 11.013 −76.333 2.582 1.00 56.66 O ATOM 1621 O HOH G 19 12.691 −69.042 −15.651 1.00 42.53 O ATOM 1622 O HOH G 20 16.776 −57.005 −13.259 1.00 46.26 O ATOM 1623 O HOH G 21 11.581 −56.209 1.044 1.00 42.54 O ATOM 1624 O HOH G 22 15.940 −62.084 1.839 1.00 50.28 O ATOM 1625 O HOH G 23 6.480 −48.205 −7.968 1.00 57.43 O ATOM 1626 O HOH G 24 39.197 −43.575 −30.519 1.00 42.04 O ATOM 1627 O HOH G 25 6.027 −62.306 −15.788 1.00 55.55 O ATOM 1628 O HOH G 26 −3.802 −54.617 −6.208 1.00 62.40 O ATOM 1629 O HOH G 27 28.505 −47.616 −34.361 1.00 65.78 O ATOM 1630 OW0 HOH G 28 −1.801 −59.317 −5.575 1.00 44.97 O ATOM 1631 OW0 HOH G 29 22.373 −53.791 −42.746 1.00 56.53 O ATOM 1632 O HOH G 30 20.463 −67.986 −5.108 1.00 49.86 O ATOM 1633 OW0 HOH G 31 1.458 −52.674 −5.845 1.00 35.48 O ATOM 1634 OW0 HOH G 32 −0.601 −51.527 −2.029 1.00 56.79 O ATOM 1635 OW0 HOH G 33 −0.725 −51.609 −7.206 1.00 46.34 O ATOM 1636 OW0 HOH G 34 52.333 −52.336 −32.501 0.33 62.20 O ATOM 1637 OW0 HOH G 35 40.005 −46.339 −20.411 1.00 51.61 O ATOM 1638 OW0 HOH G 36 7.348 −45.031 −11.009 1.00 67.53 O ATOM 1639 OW0 HOH G 37 18.638 −47.155 −44.937 1.00 42.78 O ATOM 1640 OW0 HOH G 38 42.297 −46.265 −36.401 1.00 59.51 O ATOM 1641 OW0 HOH G 39 19.312 −49.538 −53.973 1.00 63.11 O ATOM 1642 OW0 HOH G 40 12.092 −61.018 2.812 1.00 57.91 O ATOM 1643 OW0 HOH G 41 9.109 −62.096 4.871 1.00 64.80 O ATOM 1644 OW0 HOH G 42 22.011 −46.105 −39.823 1.00 57.86 O ATOM 1645 OW0 HOH G 43 46.973 −55.321 −35.496 1.00 69.49 O ATOM 1646 OW0 HOH G 44 5.887 −57.239 −20.655 1.00 60.45 O ATOM 1647 OW0 HOH G 45 3.287 −69.706 −1.459 1.00 73.57 O ATOM 1648 OW0 HOH G 46 49.236 −55.611 −31.052 1.00 63.34 O ATOM 1649 O HOH G 47 14.454 −67.301 −14.382 1.00 34.21 O ATOM 1650 OW0 HOH G 48 9.238 −74.111 −6.684 1.00 57.89 O ATOM 1651 OW0 HOH G 49 21.087 −49.042 −50.373 1.00 56.92 O ATOM 1652 OW0 HOH G 50 2.130 −50.654 −4.091 1.00 57.03 O ATOM 1653 OW0 HOH G 51 6.952 −49.477 −5.064 1.00 65.41 O ATOM 1654 OW0 HOH G 52 5.018 −51.449 −3.965 1.00 48.62 O ATOM 1655 OW0 HOH G 53 9.445 −55.961 −16.924 1.00 35.37 O ATOM 1656 OW0 HOH G 54 8.917 −72.072 −5.125 1.00 50.93 O ATOM 1657 OW0 HOH G 55 10.673 −58.107 3.325 1.00 64.30 O ATOM 1658 OW0 HOH G 56 4.127 −64.321 4.681 1.00 55.09 O ATOM 1659 OW0 HOH G 57 14.339 −57.713 0.092 1.00 64.04 O ATOM 1660 O HOH G 58 15.953 −51.995 −59.077 1.00 72.95 O ATOM 1661 OW0 HOH G 59 1.655 −62.800 −12.959 1.00 51.50 O ATOM 1662 OW0 HOH G 60 8.303 −67.621 −12.206 1.00 46.64 O ATOM 1663 OW0 HOH G 61 11.164 −52.340 1.370 1.00 66.16 O ATOM 1664 OW0 HOH G 62 7.352 −56.599 −17.979 1.00 53.67 O ATOM 1665 OW0 HOH G 63 12.595 −76.194 9.847 0.33 37.05 O ATOM 1666 OW0 HOH G 64 23.621 −44.970 −49.242 1.00 67.29 O ATOM 1667 O HOH G 65 16.972 −53.121 −66.418 1.00 85.95 O ATOM 1668 OW0 HOH G 66 3.059 −73.144 3.863 1.00 62.75 O ATOM 1669 O HOH G 67 7.859 −48.330 −32.956 1.00 65.26 O ATOM 1670 O HOH G 68 4.156 −58.856 −27.809 1.00 57.36 O ATOM 1671 O HOH G 69 4.551 −59.395 −29.922 1.00 69.10 O ATOM 1672 O HOH G 70 6.260 −47.543 −31.586 1.00 68.61 O ATOM 1673 O HOH G 71 7.840 −44.030 −28.246 1.00 62.70 O ATOM 1674 O HOH G 72 8.079 −41.411 −33.214 1.00 72.05 O ATOM 1675 O HOH G 73 5.110 −39.116 −28.229 1.00 87.18 O ATOM 1676 O HOH G 74 4.809 −40.681 −30.664 1.00 89.65 O ATOM 1677 O HOH G 75 1.648 −46.036 −34.526 1.00 82.70 O ATOM 1678 O HOH G 76 22.388 −44.026 −33.664 1.00 58.55 O ATOM 1679 O HOH G 77 29.957 −41.672 −33.880 1.00 62.69 O ATOM 1680 O HOH G 78 5.207 −64.324 −10.143 1.00 37.85 O ATOM 1681 O HOH G 79 12.766 −53.130 −50.860 1.00 46.09 O ATOM 1682 O HOH G 80 15.500 −53.938 −50.088 1.00 60.49 O ATOM 1683 O HOH G 81 8.596 −38.206 −69.322 1.00 46.24 O ATOM 1684 O HOH G 82 15.672 −67.848 −17.578 1.00 40.99 O ATOM 1685 O HOH G 83 19.615 −63.969 −15.881 1.00 30.41 O ATOM 1686 O HOH G 84 18.094 −66.902 −18.047 0.33 37.23 O ATOM 1687 OW0 HOH G 85 11.250 −67.176 −16.147 1.00 44.94 O ATOM 1688 OW0 HOH G 86 25.393 −63.667 −6.384 1.00 67.71 O ATOM 1689 OW0 HOH G 87 −1.170 −60.898 −7.473 1.00 60.19 O ATOM 1690 OW0 HOH G 88 −1.923 −60.821 −9.510 1.00 55.99 O ATOM 1691 O HOH G 89 5.204 −75.045 −0.805 1.00 66.56 O ATOM 1692 O HOH G 90 16.440 −51.952 −56.650 1.00 53.69 O ATOM 1693 O HOH G 91 17.250 −43.149 −41.268 1.00 40.84 O ATOM 1694 O HOH G 92 20.290 −55.786 2.319 1.00 69.16 O ATOM 1695 O HOH G 93 −3.677 −57.411 −6.324 1.00 55.59 O ATOM 1696 O HOH G 94 6.045 −75.775 1.785 1.00 89.59 O ATOM 1697 O HOH G 95 4.531 −53.450 −35.339 1.00 92.62 O ATOM 1698 O HOH G 96 4.130 −51.404 −33.734 1.00 82.09 O ATOM 1699 O HOH G 97 12.647 −72.205 12.644 0.33 78.15 O ATOM 1700 O HOH G 98 2.444 −62.657 4.285 1.00 59.37 O ATOM 1701 O HOH G 99 7.480 −44.064 −63.567 1.00 62.36 O ATOM 1702 O HOH H 1 10.235 −73.923 −12.362 1.00 54.56 O ATOM 1703 O HOH H 2 10.853 −75.041 −11.353 0.33 24.04 O ATOM 1704 O HOH H 3 15.894 −53.237 1.991 1.00 93.97 O ATOM 1705 O HOH H 4 39.197 −44.633 −37.978 1.00 63.14 O ATOM 1706 O HOH H 5 44.373 −55.060 −35.376 1.00 52.81 O ATOM 1707 O HOH H 6 17.661 −71.389 −5.588 1.00 43.35 O ATOM 1708 O HOH H 7 12.422 −42.244 −65.541 1.00 57.13 O ATOM 1709 O HOH H 8 6.038 −58.327 −16.631 1.00 68.30 O ATOM 1710 O HOH H 9 5.301 −73.350 5.416 1.00 76.92 O ATOM 1711 O HOH H 10 23.492 −43.612 −31.618 1.00 75.36 O ATOM 1712 O HOH H 11 26.685 −40.784 −24.862 1.00 60.70 O ATOM 1713 O HOH H 12 19.317 −64.666 6.838 1.00 65.00 O ATOM 1714 O HOH H 13 27.223 −42.773 −28.000 1.00 68.99 O ATOM 1715 O HOH H 14 1.887 −64.499 −0.652 1.00 57.61 O END

TABLE II co-ordinates with GSH HEADER --- XX-XXX-9- dasm COMPND --- REMARK 3 REMARK 3 REFINEMENT. REMARK 3  PROGRAM : REFMAC 5.2.0019 REMARK 3  AUTHORS : MURSHUDOV, VAGIN, DODSON REMARK 3 REMARK 3   REFINEMENT TARGET : MAXIMUM LIKELIHOOD REMARK 3 REMARK 3  DATA USED IN REFINEMENT. REMARK 3  RESOLUTION RANGE HIGH (ANGSTROMS) :  2.15 REMARK 3  RESOLUTION RANGE LOW (ANGSTROMS) :  49.03 REMARK 3  DATA CUTOFF (SIGMA(F)) : NONE REMARK 3  COMPLETENESS FOR RANGE (%) :  99.66 REMARK 3  NUMBER OF REFLECTIONS :  20920 REMARK 3 REMARK 3  FIT TO DATA USED IN REFINEMENT. REMARK 3  CROSS-VALIDATION METHOD : THROUGHOUT REMARK 3  FREE R VALUE TEST SET SELECTION : RANDOM REMARK 3  R VALUE (WORKING + TEST SET) : 0.18490 REMARK 3  R VALUE (WORKING SET) :  0.18301 REMARK 3  FREE R VALUE :  0.22024 REMARK 3  FREE R VALUE TEST SET SIZE (%) :  5.1 REMARK 3  FREE R VALUE TEST SET COUNT :  1129 REMARK 3 REMARK 3  FIT IN THE HIGHEST RESOLUTION BIN. REMARK 3  TOTAL NUMBER OF BINS USED :    20 REMARK 3  BIN RESOLUTION RANGE HIGH :   2.153 REMARK 3  BIN RESOLUTION RANGE LOW :   2.209 REMARK 3  REFLECTION IN BIN (WORKING SET) :   1544 REMARK 3  BIN COMPLETENESS (WORKING + TEST) (%) :  100.00 REMARK 3  BIN R VALUE (WORKING SET) :  0.245 REMARK 3  BIN FREE R VALUE SET COUNT :    93 REMARK 3  BIN FREE R VALUE :  0.264 REMARK 3 REMARK 3 NUMBER OF NON-HYDROGEN ATOMS USED IN REFINEMENT. REMARK 3  ALL ATOMS :   1444 REMARK 3 REMARK 3  B VALUES. REMARK 3  FROM WILSON PLOT (A**2) : NULL REMARK 3  MEAN B VALUE (OVERALL, A**2) :  21.523 REMARK 3  OVERALL ANISOTROPIC B VALUE. REMARK 3   B11 (A**2) : NULL REMARK 3   B22 (A**2) : NULL REMARK 3   B33 (A**2) : NULL REMARK 3   B12 (A**2) : NULL REMARK 3   B13 (A**2) : NULL REMARK 3   B23 (A**2) : NULL REMARK 3 REMARK 3  ESTIMATED OVERALL COORDINATE ERROR. REMARK 3  ESU BASED ON R VALUE (A): 0.124 REMARK 3  ESU BASED ON FREE R VALUE (A): 0.127 REMARK 3  ESU BASED ON MAXIMUM LIKELIHOOD (A): 0.099 REMARK 3  ESU FOR B VALUES BASED ON MAXIMUM LIKELIHOOD (A**2): 7.431 REMARK 3 REMARK 3 CORRELATION COEFFICIENTS. REMARK 3  CORRELATION COEFFICIENT FO-FC :  0.942 REMARK 3  CORRELATION COEFFICIENT FO-FC FREE :  0.921 REMARK 3 REMARK 3  RMS DEVIATIONS FROM IDEAL VALUES COUNT  RMS  WEIGHT REMARK 3  BOND LENGTHS REFINED ATOMS (A):  1346 ; 0.025 ; 0.021 REMARK 3  BOND ANGLES REFINED ATOMS (DEGREES):  1811 ; 2.485 ; 2.033 REMARK 3  TORSION ANGLES, PERIOD 1 (DEGREES):  153 ; 6.375 ; 5.000 REMARK 3  TORSION ANGLES, PERIOD 2 (DEGREES):   52 ;29.194 ;19.808 REMARK 3  TORSION ANGLES, PERIOD 3 (DEGREES):  182 ;17.505 ;15.000 REMARK 3  TORSION ANGLES, PERIOD 4 (DEGREES):   13 ;19.279 ;15.000 REMARK 3  CHIRAL-CENTER RESTRAINTS (A**3):  205 ; 0.216 ; 0.200 REMARK 3  GENERAL PLANES REFINED ATOMS (A):  963 ; 0.011 ; 0.020 REMARK 3  NON-BONDED CONTACTS REFINED ATOMS (A):  583 ; 0.238 ; 0.200 REMARK 3  NON-BONDED TORSION REFINED ATOMS (A):  892 ; 0.317 ; 0.200 REMARK 3  H-BOND (X...Y) REFINED ATOMS (A):   75 ; 0.383 ; 0.200 REMARK 3  SYMMETRY VDW REFINED ATOMS (A):  102 ; 0.227 ; 0.200 REMARK 3  SYMMETRY H-BOND REFINED ATOMS (A):   33 ; 0.213 ; 0.200 REMARK 3 REMARK 3  ISOTROPIC THERMAL FACTOR RESTRAINTS.  COUNT  RMS  WEIGHT REMARK 3  MAIN-CHAIN BOND REFINED ATOMS (A**2):  777 ; 1.310 ; 1.500 REMARK 3  MAIN-CHAIN ANGLE REFINED ATOMS (A**2):  1199 ; 1.935 ; 2.000 REMARK 3  SIDE-CHAIN BOND REFINED ATOMS (A**2):  637 ; 3.354 ; 3.000 REMARK 3  SIDE-CHAIN ANGLE REFINED ATOMS (A**2):  610 ; 4.793 ; 4.500 REMARK 3 REMARK 3  NCS RESTRAINTS STATISTICS REMARK 3  NUMBER OF NCS GROUPS : NULL REMARK 3 REMARK 3 REMARK 3  TLS DETAILS REMARK 3  NUMBER OF TLS GROUPS  :   4 REMARK 3  ATOM RECORD CONTAINS RESIDUAL B FACTORS ONLY REMARK 3 REMARK 3  TLS GROUP  :   1 REMARK 3   NUMBER OF COMPONENTS GROUP  :    1 REMARK 3   COMPONENTS C SSSEQI TO C SSSEQI REMARK 3   RESIDUE RANGE : A   −4 A   4 REMARK 3   ORIGIN FOR THE GROUP (A):  38.7610  30.7943  37.1686 REMARK 3   T TENSOR REMARK 3    T11: 0.0263 T22: 0.0132 REMARK 3    T33: −0.0026 T12: −0.0504 REMARK 3    T13: −0.1743 T23: 0.0166 REMARK 3   L TENSOR REMARK 3    L11: 43.7540 L22: 14.5336 REMARK 3    L33: 8.4265 L12: 22.5082 REMARK 3    L13: −4.8297 L23: −2.5635 REMARK 3   S TENSOR REMARK 3    S11: 0.4125 S12: 0.0342 S13: 0.0464 REMARK 3    S21: 0.5494 S22: −0.3780 S23: −0.3859 REMARK 3    S31: 0.4718 S32: 0.7522 S33: −0.0345 REMARK 3 REMARK 3  TLS GROUP  :   2 REMARK 3   NUMBER OF COMPONENTS GROUP  :    1 REMARK 3   COMPONENTS C SSSEQI TO C SSSEQI REMARK 3   RESIDUE RANGE : A   5 A   47 REMARK 3   ORIGIN FOR THE GROUP (A):  18.6917   4.7881  21.1784 REMARK 3   T TENSOR REMARK 3    T11: 0.0778 T22: 0.0210 REMARK 3    T33: 0.0780 T12: −0.0304 REMARK 3    T13: 0.0112 T23: −0.0223 REMARK 3   L TENSOR REMARK 3    L11: 1.6369 L22: 2.6248 REMARK 3    L33: 3.7651 L12: 1.4943 REMARK 3    L13: 1.4586 L23: 1.8919 REMARK 3   S TENSOR REMARK 3    S11: 0.0517 S12: −0.0060 S13: −0.2508 REMARK 3    S21: 0.1396 S22: −0.0663 S23: −0.0501 REMARK 3    S31: 0.5843 S32: −0.1539 S33: 0.0146 REMARK 3 REMARK 3  TLS GROUP  :   3 REMARK 3   NUMBER OF COMPONENTS GROUP  :    1 REMARK 3   COMPONENTS C SSSEQI TO C SSSEQI REMARK 3   RESIDUE RANGE : A   48 A  108 REMARK 3   ORIGIN FOR THE GROUP (A):  13.6553  14.2035  29.6632 REMARK 3   T TENSOR REMARK 3    T11: 0.0402 T22: 0.0368 REMARK 3    T33: 0.0374 T12: −0.0427 REMARK 3    T13: −0.0076 T23: −0.0064 REMARK 3   L TENSOR REMARK 3    L11: 1.3293 L22: 2.4856 REMARK 3    L33: 1.2819 L12: 1.1540 REMARK 3    L13: 0.8262 L23: 1.2899 REMARK 3   S TENSOR REMARK 3    S11: 0.0470 S12: −0.1247 S13: −0.0343 REMARK 3    S21: 0.1694 S22: −0.0326 S23: 0.0912 REMARK 3    S31: 0.1021 S32: −0.1147 S33: −0.0143 REMARK 3 REMARK 3  TLS GROUP  :   4 REMARK 3   NUMBER OF COMPONENTS GROUP  :    1 REMARK 3   COMPONENTS C SSSEQI TO C SSSEQI REMARK 3   RESIDUE RANGE : A  109 A  145 REMARK 3   ORIGIN FOR THE GROUP (A):  11.7672  39.2439  35.7931 REMARK 3   T TENSOR REMARK 3    T11: 0.0948 T22: 0.1006 REMARK 3    T33: 0.1232 T12: 0.0341 REMARK 3    T13: −0.0316 T23: −0.0639 REMARK 3   L TENSOR REMARK 3    L11: 0.7275 L22: 19.7339 REMARK 3    L33: 1.6059 L12: 3.7802 REMARK 3    L13: 0.6232 L23: 2.9231 REMARK 3   S TENSOR REMARK 3    S11: −0.1412 S12: −0.0355 S13: 0.2319 REMARK 3    S21: 0.0911 S22: −0.0196 S23: 1.1691 REMARK 3    S31: −0.2654 S32: −0.1500 S33: 0.1608 REMARK 3 REMARK 3 REMARK 3  BULK SOLVENT MODELLING. REMARK 3  METHOD USED :  MASK REMARK 3  PARAMETERS FOR MASK CALCULATION REMARK 3  VDW PROBE RADIUS :  1.20 REMARK 3  ION PROBE RADIUS :  0.80 REMARK 3  SHRINKAGE RADIUS :  0.80 REMARK 3 REMARK 3  OTHER REFINEMENT REMARKS: REMARK 3  HYDROGENS HAVE BEEN ADDED IN THE RIDING POSITIONS REMARK 3 CISPEP 1 HIS A −4 HIS A −3 0.00 CISPEP 2 PRO A 37 PRO A 38 0.00 CRYST1 169.940 169.940 169.940 90.00   90.00  90.00 F 2 3 SCALE1 0.005884 0.000000 0.000000 0.00000 SCALE2 0.000000 0.005884 0.000000 0.00000 SCALE3 0.000000 0.000000 0.005884 0.00000 ATOM 1 N HIS A −4 45.102 31.739 30.742 1.00 43.85 N ATOM 2 CA HIS A −4 44.912 32.035 32.222 1.00 44.81 C ATOM 3 CB HIS A −4 46.047 31.383 33.039 1.00 43.72 C ATOM 4 CG HIS A −4 47.334 32.147 32.989 1.00 42.63 C ATOM 5 ND1 HIS A −4 48.139 32.175 31.872 1.00 41.37 N ATOM 6 CE1 HIS A −4 49.193 32.937 32.107 1.00 39.60 C ATOM 7 NE2 HIS A −4 49.092 33.413 33.334 1.00 39.25 N ATOM 8 CD2 HIS A −4 47.941 32.935 33.911 1.00 39.51 C ATOM 9 C HIS A −4 44.952 33.568 32.414 1.00 45.14 C ATOM 10 O HIS A −4 45.605 34.238 31.607 1.00 46.36 O ATOM 11 N HIS A −3 44.343 34.189 33.435 1.00 45.00 N ATOM 12 CA HIS A −3 43.545 33.720 34.595 1.00 44.05 C ATOM 13 CB HIS A −3 42.075 33.507 34.265 1.00 43.76 C ATOM 14 CG HIS A −3 41.624 34.373 33.110 1.00 45.31 C ATOM 15 ND1 HIS A −3 41.585 35.756 33.185 1.00 44.37 N ATOM 16 CE1 HIS A −3 41.234 36.246 32.006 1.00 44.90 C ATOM 17 NE2 HIS A −3 41.048 35.237 31.168 1.00 41.90 N ATOM 18 CD2 HIS A −3 41.330 34.060 31.815 1.00 42.23 C ATOM 19 C HIS A −3 44.138 33.078 35.875 1.00 44.08 C ATOM 20 O HIS A −3 44.669 31.928 35.919 1.00 44.84 O ATOM 21 N HIS A −2 44.069 33.881 36.929 1.00 41.86 N ATOM 22 CA HIS A −2 44.313 33.388 38.250 1.00 40.21 C ATOM 23 CB HIS A −2 45.268 34.314 38.943 1.00 39.35 C ATOM 24 CG HIS A −2 46.603 34.281 38.312 1.00 38.72 C ATOM 25 ND1 HIS A −2 47.659 33.571 38.846 1.00 40.91 N ATOM 26 CE1 HIS A −2 48.706 33.695 38.054 1.00 39.34 C ATOM 27 NE2 HIS A −2 48.346 34.412 37.003 1.00 40.80 N ATOM 28 CD2 HIS A −2 47.036 34.792 37.139 1.00 36.98 C ATOM 29 C HIS A −2 43.028 33.183 39.024 1.00 39.93 C ATOM 30 O HIS A −2 43.058 33.196 40.260 1.00 40.14 O ATOM 31 N HIS A −1 41.913 33.024 38.295 1.00 38.27 N ATOM 32 CA HIS A −1 40.687 32.426 38.860 1.00 38.31 C ATOM 33 CB HIS A −1 39.796 33.479 39.494 1.00 37.44 C ATOM 34 CG HIS A −1 39.148 34.364 38.481 1.00 37.49 C ATOM 35 ND1 HIS A −1 39.820 35.414 37.880 1.00 32.64 N ATOM 36 CE1 HIS A −1 39.015 35.995 37.011 1.00 31.75 C ATOM 37 NE2 HIS A −1 37.858 35.346 37.008 1.00 34.18 N ATOM 38 CD2 HIS A −1 37.926 34.302 37.900 1.00 31.68 C ATOM 39 C HIS A −1 39.917 31.681 37.776 1.00 37.15 C ATOM 40 O HIS A −1 40.095 31.915 36.568 1.00 38.15 O ATOM 41 N HIS A 0 39.041 30.787 38.195 1.00 37.14 N ATOM 42 CA HIS A 0 38.185 30.098 37.211 1.00 36.62 C ATOM 43 CB HIS A 0 38.679 28.671 36.986 1.00 37.80 C ATOM 44 CG HIS A 0 38.516 27.796 38.199 1.00 42.93 C ATOM 45 ND1 HIS A 0 39.575 27.442 39.018 1.00 48.02 N ATOM 46 CE1 HIS A 0 39.128 26.685 40.012 1.00 50.57 C ATOM 47 NE2 HIS A 0 37.812 26.555 39.882 1.00 49.00 N ATOM 48 CD2 HIS A 0 37.404 27.257 38.769 1.00 45.61 C ATOM 49 C HIS A 0 36.760 30.045 37.746 1.00 35.43 C ATOM 50 O HIS A 0 36.554 30.184 38.965 1.00 36.72 O ATOM 51 N HIS A 1 35.775 29.837 36.882 1.00 32.02 N ATOM 52 CA HIS A 1 34.422 29.832 37.358 1.00 30.71 C ATOM 53 CB HIS A 1 33.572 30.843 36.606 1.00 30.18 C ATOM 54 CG HIS A 1 33.987 32.271 36.831 1.00 30.69 C ATOM 55 ND1 HIS A 1 33.424 33.069 37.801 1.00 30.91 N ATOM 56 CE1 HIS A 1 33.990 34.258 37.790 1.00 25.35 C ATOM 57 NE2 HIS A 1 34.887 34.273 36.824 1.00 30.30 N ATOM 58 CD2 HIS A 1 34.892 33.046 36.197 1.00 25.86 C ATOM 59 C HIS A 1 33.806 28.427 37.249 1.00 30.57 C ATOM 60 O HIS A 1 32.588 28.307 37.257 1.00 29.93 O ATOM 61 N LYS A 2 34.646 27.397 37.102 1.00 30.64 N ATOM 62 CA LYS A 2 34.236 26.005 37.051 1.00 31.42 C ATOM 63 CB LYS A 2 35.434 25.072 37.010 1.00 30.60 C ATOM 64 CG LYS A 2 36.165 24.993 35.743 1.00 29.46 C ATOM 65 CD LYS A 2 37.227 23.927 35.908 1.00 26.47 C ATOM 66 CE LYS A 2 38.440 24.557 36.561 1.00 26.15 C ATOM 67 NZ LYS A 2 39.414 23.476 36.821 1.00 28.93 N ATOM 68 C LYS A 2 33.467 25.601 38.282 1.00 31.29 C ATOM 69 O LYS A 2 32.553 24.762 38.175 1.00 30.92 O ATOM 70 N ASP A 3 33.856 26.142 39.447 1.00 30.40 N ATOM 71 CA ASP A 3 33.168 25.781 40.677 1.00 31.15 C ATOM 72 CB ASP A 3 34.018 26.017 41.953 1.00 32.15 C ATOM 73 CG ASP A 3 34.650 27.445 42.017 1.00 39.24 C ATOM 74 OD1 ASP A 3 34.454 28.282 41.071 1.00 38.35 O ATOM 75 OD2 ASP A 3 35.390 27.696 43.034 1.00 45.40 O ATOM 76 C ASP A 3 31.764 26.410 40.747 1.00 29.46 C ATOM 77 O ASP A 3 30.992 26.115 41.626 1.00 28.62 O ATOM 78 N GLU A 4 31.409 27.245 39.789 1.00 28.05 N ATOM 79 CA GLU A 4 30.030 27.750 39.760 1.00 27.71 C ATOM 80 CB GLU A 4 30.027 29.190 39.258 1.00 29.09 C ATOM 81 CG GLU A 4 31.112 30.021 39.957 1.00 34.58 C ATOM 82 CD GLU A 4 30.816 31.477 39.858 1.00 41.79 C ATOM 83 OE1 GLU A 4 29.818 31.830 40.492 1.00 47.49 O ATOM 84 OE2 GLU A 4 31.547 32.257 39.179 1.00 41.63 O ATOM 85 C GLU A 4 29.073 26.917 38.913 1.00 25.13 C ATOM 86 O GLU A 4 27.869 27.176 38.941 1.00 25.62 O ATOM 87 N VAL A 5 29.605 25.972 38.122 1.00 21.53 N ATOM 88 CA VAL A 5 28.807 25.259 37.104 1.00 18.86 C ATOM 89 CB VAL A 5 28.989 25.880 35.687 1.00 18.68 C ATOM 90 CG1 VAL A 5 28.636 27.341 35.687 1.00 18.92 C ATOM 91 CG2 VAL A 5 30.479 25.719 35.207 1.00 15.79 C ATOM 92 C VAL A 5 29.099 23.739 37.029 1.00 16.85 C ATOM 93 O VAL A 5 28.712 23.086 36.068 1.00 16.80 O ATOM 94 N ALA A 6 29.807 23.186 38.015 1.00 15.69 N ATOM 95 CA ALA A 6 30.302 21.815 37.911 1.00 14.08 C ATOM 96 CB ALA A 6 31.464 21.535 38.950 1.00 11.02 C ATOM 97 C ALA A 6 29.156 20.840 38.117 1.00 13.46 C ATOM 98 O ALA A 6 29.185 19.787 37.499 1.00 14.39 O ATOM 99 N LEU A 7 28.173 21.164 38.968 1.00 13.42 N ATOM 100 CA LEU A 7 26.929 20.360 39.068 1.00 13.82 C ATOM 101 CB LEU A 7 25.970 20.812 40.176 1.00 13.27 C ATOM 102 CG LEU A 7 26.539 20.898 41.588 1.00 13.97 C ATOM 103 CD1 LEU A 7 25.510 21.510 42.558 1.00 11.74 C ATOM 104 CD2 LEU A 7 26.941 19.510 42.092 1.00 14.06 C ATOM 105 C LEU A 7 26.157 20.363 37.773 1.00 14.03 C ATOM 106 O LEU A 7 25.619 19.330 37.352 1.00 13.31 O ATOM 107 N LEU A 8 26.044 21.537 37.145 1.00 14.06 N ATOM 108 CA LEU A 8 25.348 21.637 35.864 1.00 13.18 C ATOM 109 CB LEU A 8 25.335 23.115 35.414 1.00 13.77 C ATOM 110 CG LEU A 8 24.715 24.164 36.346 1.00 14.55 C ATOM 111 CD1 LEU A 8 24.831 25.603 35.752 1.00 8.94 C ATOM 112 CD2 LEU A 8 23.234 23.801 36.798 1.00 7.45 C ATOM 113 C LEU A 8 26.074 20.800 34.774 1.00 13.11 C ATOM 114 O LEU A 8 25.471 20.178 33.900 1.00 13.24 O ATOM 115 N ALA A 9 27.404 20.811 34.848 1.00 14.33 N ATOM 116 CA ALA A 9 28.227 20.131 33.903 1.00 14.51 C ATOM 117 CB ALA A 9 29.656 20.601 34.001 1.00 12.38 C ATOM 118 C ALA A 9 28.086 18.596 34.127 1.00 14.24 C ATOM 119 O ALA A 9 28.023 17.845 33.123 1.00 12.19 O ATOM 120 N ALA A 10 28.057 18.157 35.399 1.00 14.37 N ATOM 121 CA ALA A 10 27.853 16.756 35.760 1.00 14.67 C ATOM 122 CB ALA A 10 28.007 16.541 37.242 1.00 13.11 C ATOM 123 C ALA A 10 26.473 16.242 35.283 1.00 15.35 C ATOM 124 O ALA A 10 26.348 15.103 34.823 1.00 15.31 O ATOM 125 N VAL A 11 25.432 17.036 35.483 1.00 15.32 N ATOM 126 CA VAL A 11 24.056 16.637 35.058 1.00 14.33 C ATOM 127 CB VAL A 11 22.961 17.570 35.666 1.00 12.15 C ATOM 128 CG1 VAL A 11 21.549 17.348 35.037 1.00 10.49 C ATOM 129 CG2 VAL A 11 22.898 17.323 37.227 1.00 12.81 C ATOM 130 C VAL A 11 23.989 16.614 33.528 1.00 17.02 C ATOM 131 O VAL A 11 23.308 15.756 32.932 1.00 16.98 O ATOM 132 N THR A 12 24.708 17.563 32.894 1.00 15.77 N ATOM 133 CA THR A 12 24.798 17.603 31.426 1.00 16.21 C ATOM 134 CB THR A 12 25.658 18.831 30.969 1.00 16.10 C ATOM 135 OG1 THR A 12 24.986 20.020 31.391 1.00 13.83 O ATOM 136 CG2 THR A 12 25.864 18.845 29.446 1.00 15.32 C ATOM 137 C THR A 12 25.452 16.327 30.874 1.00 16.28 C ATOM 138 O THR A 12 24.927 15.733 29.922 1.00 16.08 O ATOM 139 N LEU A 13 26.563 15.918 31.478 1.00 13.10 N ATOM 140 CA LEU A 13 27.250 14.704 31.126 1.00 14.57 C ATOM 141 CB LEU A 13 28.630 14.631 31.829 1.00 12.99 C ATOM 142 CG LEU A 13 29.387 13.383 31.346 1.00 18.22 C ATOM 143 CD1 LEU A 13 29.645 13.517 29.809 1.00 15.91 C ATOM 144 CD2 LEU A 13 30.658 13.091 32.099 1.00 18.98 C ATOM 145 C LEU A 13 26.400 13.425 31.344 1.00 15.67 C ATOM 146 O LEU A 13 26.334 12.543 30.496 1.00 16.15 O ATOM 147 N LEU A 14 25.744 13.339 32.467 1.00 16.66 N ATOM 148 CA LEU A 14 24.770 12.300 32.680 1.00 18.79 C ATOM 149 CB LEU A 14 24.153 12.435 34.071 1.00 18.03 C ATOM 150 CG LEU A 14 23.125 11.381 34.470 1.00 24.54 C ATOM 151 CD1 LEU A 14 23.749 9.964 34.585 1.00 25.47 C ATOM 152 CD2 LEU A 14 22.496 11.762 35.815 1.00 22.08 C ATOM 153 C LEU A 14 23.688 12.262 31.600 1.00 19.00 C ATOM 154 O LEU A 14 23.298 11.169 31.197 1.00 19.10 O ATOM 155 N GLY A 15 23.167 13.433 31.199 1.00 19.54 N ATOM 156 CA GLY A 15 22.243 13.576 30.078 1.00 18.51 C ATOM 157 C GLY A 15 22.743 12.983 28.750 1.00 18.18 C ATOM 158 O GLY A 15 21.981 12.279 28.077 1.00 18.00 O ATOM 159 N VAL A 16 24.009 13.250 28.391 1.00 14.62 N ATOM 160 CA VAL A 16 24.608 12.764 27.214 1.00 14.16 C ATOM 161 CB VAL A 16 26.071 13.433 26.960 1.00 15.20 C ATOM 162 CG1 VAL A 16 26.823 12.670 25.920 1.00 12.26 C ATOM 163 CG2 VAL A 16 25.907 14.937 26.582 1.00 12.65 C ATOM 164 C VAL A 16 24.735 11.252 27.250 1.00 13.94 C ATOM 165 O VAL A 16 24.485 10.577 26.225 1.00 13.45 O ATOM 166 N LEU A 17 25.155 10.713 28.413 1.00 12.68 N ATOM 167 CA LEU A 17 25.238 9.280 28.592 1.00 13.23 C ATOM 168 CB LEU A 17 25.798 8.914 29.967 1.00 11.56 C ATOM 169 CG LEU A 17 27.292 9.195 30.095 1.00 16.23 C ATOM 170 CD1 LEU A 17 27.690 9.247 31.608 1.00 14.52 C ATOM 171 CD2 LEU A 17 28.121 8.165 29.346 1.00 14.49 C ATOM 172 C LEU A 17 23.905 8.591 28.455 1.00 12.70 C ATOM 173 O LEU A 17 23.843 7.464 27.959 1.00 11.56 O ATOM 174 N LEU A 18 22.845 9.204 29.014 1.00 12.69 N ATOM 175 CA LEU A 18 21.508 8.664 28.834 1.00 14.20 C ATOM 176 CB LEU A 18 20.522 9.499 29.635 1.00 13.39 C ATOM 177 CG LEU A 18 19.122 8.880 29.823 1.00 19.24 C ATOM 178 CD1 LEU A 18 19.090 7.475 30.542 1.00 18.85 C ATOM 179 CD2 LEU A 18 18.112 9.948 30.464 1.00 16.88 C ATOM 180 C LEU A 18 21.088 8.637 27.323 1.00 12.86 C ATOM 181 O LEU A 18 20.470 7.683 26.877 1.00 14.91 O ATOM 182 N GLN A 19 21.372 9.701 26.567 1.00 12.79 N ATOM 183 CA GLN A 19 21.004 9.815 25.141 1.00 14.03 C ATOM 184 CB GLN A 19 21.365 11.183 24.568 1.00 13.85 C ATOM 185 CG GLN A 19 20.385 12.290 25.041 1.00 13.14 C ATOM 186 CD GLN A 19 18.902 12.058 24.662 1.00 17.44 C ATOM 187 OE1 GLN A 19 18.030 12.114 25.511 1.00 18.58 O ATOM 188 NE2 GLN A 19 18.636 11.780 23.422 1.00 11.71 N ATOM 189 C GLN A 19 21.823 8.766 24.366 1.00 13.92 C ATOM 190 O GLN A 19 21.270 8.116 23.515 1.00 15.23 O ATOM 191 N ALA A 20 23.085 8.528 24.761 1.00 13.14 N ATOM 192 CA ALA A 20 23.928 7.510 24.165 1.00 13.90 C ATOM 193 CB ALA A 20 25.334 7.530 24.801 1.00 12.18 C ATOM 194 C ALA A 20 23.260 6.095 24.341 1.00 14.12 C ATOM 195 O ALA A 20 23.175 5.317 23.410 1.00 13.96 O ATOM 196 N TYR A 21 22.827 5.807 25.553 1.00 15.22 N ATOM 197 CA TYR A 21 22.074 4.571 25.895 1.00 14.63 C ATOM 198 CB TYR A 21 21.726 4.595 27.394 1.00 12.88 C ATOM 199 CG TYR A 21 20.766 3.477 27.812 1.00 14.08 C ATOM 200 CD1 TYR A 21 21.226 2.173 27.952 1.00 12.81 C ATOM 201 CE1 TYR A 21 20.384 1.131 28.285 1.00 13.55 C ATOM 202 CZ TYR A 21 19.041 1.375 28.478 1.00 14.21 C ATOM 203 OH TYR A 21 18.284 0.289 28.855 1.00 17.59 O ATOM 204 CE2 TYR A 21 18.511 2.666 28.341 1.00 14.36 C ATOM 205 CD2 TYR A 21 19.404 3.716 27.983 1.00 12.11 C ATOM 206 C TYR A 21 20.815 4.357 24.999 1.00 14.79 C ATOM 207 O TYR A 21 20.563 3.241 24.524 1.00 15.79 O ATOM 208 N PHE A 22 20.020 5.419 24.820 1.00 13.65 N ATOM 209 CA PHE A 22 18.812 5.396 24.001 1.00 13.77 C ATOM 210 CB PHE A 22 18.101 6.784 23.979 1.00 12.79 C ATOM 211 CG PHE A 22 17.533 7.202 25.310 1.00 13.01 C ATOM 212 CD1 PHE A 22 17.200 6.234 26.299 1.00 9.44 C ATOM 213 CE1 PHE A 22 16.662 6.615 27.542 1.00 10.73 C ATOM 214 CZ PHE A 22 16.457 7.957 27.798 1.00 12.97 C ATOM 215 CE2 PHE A 22 16.818 8.940 26.800 1.00 9.75 C ATOM 216 CD2 PHE A 22 17.326 8.556 25.595 1.00 9.89 C ATOM 217 C PHE A 22 19.225 5.028 22.563 1.00 14.12 C ATOM 218 O PHE A 22 18.553 4.202 21.895 1.00 12.02 O ATOM 219 N SER A 23 20.328 5.633 22.115 1.00 13.90 N ATOM 220 CA SER A 23 20.858 5.344 20.792 1.00 14.33 C ATOM 221 CB SER A 23 22.038 6.244 20.365 1.00 13.68 C ATOM 222 OG SER A 23 21.537 7.538 20.302 1.00 22.60 O ATOM 223 C SER A 23 21.331 3.934 20.671 1.00 12.41 C ATOM 224 O SER A 23 21.106 3.315 19.649 1.00 12.71 O ATOM 225 N LEU A 24 22.063 3.424 21.637 1.00 11.34 N ATOM 226 CA LEU A 24 22.516 2.029 21.489 1.00 9.87 C ATOM 227 CB LEU A 24 23.407 1.702 22.679 1.00 10.30 C ATOM 228 CG LEU A 24 24.725 2.524 22.673 1.00 13.60 C ATOM 229 CD1 LEU A 24 25.540 2.351 24.000 1.00 11.42 C ATOM 230 CD2 LEU A 24 25.599 2.005 21.456 1.00 13.75 C ATOM 231 C LEU A 24 21.303 1.081 21.505 1.00 10.73 C ATOM 232 O LEU A 24 21.342 −0.016 20.919 1.00 9.21 O ATOM 233 N GLN A 25 20.235 1.479 22.228 1.00 10.44 N ATOM 234 CA GLN A 25 18.962 0.658 22.266 1.00 11.89 C ATOM 235 CB GLN A 25 18.054 1.091 23.443 1.00 12.09 C ATOM 236 CG GLN A 25 18.702 0.839 24.798 1.00 12.91 C ATOM 237 CD GLN A 25 18.745 −0.651 25.075 1.00 20.45 C ATOM 238 OE1 GLN A 25 19.774 −1.298 24.951 1.00 22.86 O ATOM 239 NE2 GLN A 25 17.606 −1.207 25.352 1.00 20.18 N ATOM 240 C GLN A 25 18.208 0.659 20.949 1.00 11.61 C ATOM 241 O GLN A 25 17.641 −0.349 20.541 1.00 14.14 O ATOM 242 N VAL A 26 18.185 1.786 20.257 1.00 13.41 N ATOM 243 CA VAL A 26 17.685 1.765 18.887 1.00 12.07 C ATOM 244 CB VAL A 26 17.628 3.193 18.290 1.00 13.82 C ATOM 245 CG1 VAL A 26 17.136 3.074 16.788 1.00 9.67 C ATOM 246 CG2 VAL A 26 16.680 4.017 19.099 1.00 12.85 C ATOM 247 C VAL A 26 18.531 0.829 17.964 1.00 11.93 C ATOM 248 O VAL A 26 17.966 0.078 17.174 1.00 11.16 O ATOM 249 N ILE A 27 19.874 0.927 18.006 1.00 10.57 N ATOM 250 CA ILE A 27 20.744 0.022 17.221 1.00 9.41 C ATOM 251 CB ILE A 27 22.218 0.318 17.510 1.00 8.62 C ATOM 252 CG1 ILE A 27 22.529 1.749 17.019 1.00 7.59 C ATOM 253 CD1 ILE A 27 23.899 2.314 17.344 1.00 10.48 C ATOM 254 CG2 ILE A 27 23.119 −0.792 16.846 1.00 5.42 C ATOM 255 C ILE A 27 20.391 −1.464 17.507 1.00 10.44 C ATOM 256 O ILE A 27 20.296 −2.326 16.600 1.00 11.32 O ATOM 257 N SER A 28 20.157 −1.748 18.771 1.00 10.48 N ATOM 258 CA SER A 28 19.829 −3.060 19.189 1.00 12.55 C ATOM 259 CB SER A 28 19.932 −3.099 20.723 1.00 12.29 C ATOM 260 OG SER A 28 19.487 −4.370 21.191 1.00 17.87 O ATOM 261 C SER A 28 18.422 −3.448 18.660 1.00 11.75 C ATOM 262 O SER A 28 18.199 −4.572 18.248 1.00 10.69 O ATOM 263 N ALA A 29 17.475 −2.515 18.644 1.00 12.74 N ATOM 264 CA ALA A 29 16.139 −2.833 18.067 1.00 13.62 C ATOM 265 CB ALA A 29 15.133 −1.670 18.399 1.00 13.35 C ATOM 266 C ALA A 29 16.229 −3.069 16.521 1.00 12.51 C ATOM 267 O ALA A 29 15.497 −3.835 15.967 1.00 12.55 O ATOM 268 N ARG A 30 17.148 −2.420 15.848 1.00 11.66 N ATOM 269 CA ARG A 30 17.317 −2.575 14.409 1.00 13.71 C ATOM 270 CB ARG A 30 18.356 −1.560 13.883 1.00 13.34 C ATOM 271 CG ARG A 30 17.788 −0.190 13.607 1.00 12.61 C ATOM 272 CD ARG A 30 18.745 0.766 12.913 1.00 13.07 C ATOM 273 NE ARG A 30 18.157 2.108 12.760 1.00 12.05 N ATOM 274 CZ ARG A 30 17.255 2.449 11.830 1.00 12.21 C ATOM 275 NH1 ARG A 30 16.827 1.523 10.929 1.00 7.86 N ATOM 276 NH2 ARG A 30 16.792 3.727 11.747 1.00 5.61 N ATOM 277 C ARG A 30 17.766 −3.994 14.130 1.00 15.25 C ATOM 278 O ARG A 30 17.277 −4.635 13.202 1.00 15.66 O ATOM 279 N ARG A 31 18.698 −4.480 14.957 1.00 17.22 N ATOM 280 CA ARG A 31 19.152 −5.856 14.911 1.00 20.02 C ATOM 281 CB ARG A 31 20.351 −6.058 15.855 1.00 18.29 C ATOM 282 CG ARG A 31 21.084 −7.465 15.656 1.00 26.40 C ATOM 283 CD ARG A 31 22.466 −7.540 16.418 1.00 28.12 C ATOM 284 NE ARG A 31 22.986 −6.152 16.672 1.00 44.00 N ATOM 285 CZ ARG A 31 23.816 −5.440 15.868 1.00 46.92 C ATOM 286 NH1 ARG A 31 24.296 −5.990 14.717 1.00 49.61 N ATOM 287 NH2 ARG A 31 24.186 −4.189 16.220 1.00 41.52 N ATOM 288 C ARG A 31 18.015 −6.885 15.203 1.00 18.00 C ATOM 289 O ARG A 31 17.697 −7.700 14.339 1.00 16.67 O ATOM 290 N ALA A 32 17.409 −6.835 16.403 1.00 17.87 N ATOM 291 CA ALA A 32 16.280 −7.703 16.761 1.00 17.39 C ATOM 292 CB ALA A 32 15.704 −7.291 18.143 1.00 15.94 C ATOM 293 C ALA A 32 15.170 −7.750 15.685 1.00 17.99 C ATOM 294 O ALA A 32 14.678 −8.814 15.388 1.00 18.15 O ATOM 295 N PHE A 33 14.785 −6.609 15.104 1.00 18.07 N ATOM 296 CA PHE A 33 13.641 −6.533 14.201 1.00 20.32 C ATOM 297 CB PHE A 33 12.694 −5.399 14.592 1.00 21.89 C ATOM 298 CG PHE A 33 12.162 −5.541 15.978 1.00 23.17 C ATOM 299 CD1 PHE A 33 11.065 −6.357 16.230 1.00 28.57 C ATOM 300 CE1 PHE A 33 10.593 −6.518 17.547 1.00 29.89 C ATOM 301 CZ PHE A 33 11.239 −5.884 18.591 1.00 27.38 C ATOM 302 CE2 PHE A 33 12.311 −5.029 18.334 1.00 28.15 C ATOM 303 CD2 PHE A 33 12.773 −4.889 17.038 1.00 25.87 C ATOM 304 C PHE A 33 14.036 −6.423 12.746 1.00 21.44 C ATOM 305 O PHE A 33 13.177 −6.317 11.857 1.00 22.66 O ATOM 306 N ARG A 34 15.339 −6.506 12.484 1.00 21.20 N ATOM 307 CA ARG A 34 15.819 −6.527 11.098 1.00 21.81 C ATOM 308 CB ARG A 34 15.556 −7.892 10.425 1.00 21.90 C ATOM 309 CG ARG A 34 16.064 −9.089 11.279 1.00 25.86 C ATOM 310 CD ARG A 34 16.624 −10.245 10.465 1.00 31.94 C ATOM 311 NE ARG A 34 15.585 −11.210 10.111 1.00 37.48 N ATOM 312 CZ ARG A 34 14.997 −12.057 10.967 1.00 42.81 C ATOM 313 NH1 ARG A 34 15.336 −12.039 12.268 1.00 45.32 N ATOM 314 NH2 ARG A 34 14.046 −12.913 10.528 1.00 43.06 N ATOM 315 C ARG A 34 15.291 −5.334 10.267 1.00 20.00 C ATOM 316 O ARG A 34 14.887 −5.493 9.105 1.00 22.72 O ATOM 317 N VAL A 35 15.324 −4.153 10.882 1.00 18.69 N ATOM 318 CA VAL A 35 14.985 −2.885 10.239 1.00 15.42 C ATOM 319 CB VAL A 35 14.071 −2.014 11.137 1.00 13.95 C ATOM 320 CG1 VAL A 35 13.696 −0.739 10.374 1.00 12.35 C ATOM 321 CG2 VAL A 35 12.796 −2.771 11.580 1.00 14.58 C ATOM 322 C VAL A 35 16.252 −2.122 9.891 1.00 15.66 C ATOM 323 O VAL A 35 16.864 −1.503 10.748 1.00 12.69 O ATOM 324 N SER A 36 16.661 −2.172 8.625 1.00 15.31 N ATOM 325 CA SER A 36 17.901 −1.496 8.223 1.00 17.02 C ATOM 326 CB SER A 36 18.550 −2.218 7.034 1.00 16.98 C ATOM 327 OG SER A 36 18.318 −3.599 7.163 1.00 26.41 O ATOM 328 C SER A 36 17.764 −0.054 7.778 1.00 15.01 C ATOM 329 O SER A 36 16.839 0.285 7.027 1.00 15.40 O ATOM 330 N PRO A 37 18.760 0.779 8.139 1.00 14.72 N ATOM 331 CA PRO A 37 18.760 2.133 7.551 1.00 13.18 C ATOM 332 CB PRO A 37 20.082 2.753 8.103 1.00 13.40 C ATOM 333 CG PRO A 37 20.325 2.015 9.380 1.00 12.81 C ATOM 334 CD PRO A 37 19.905 0.558 9.058 1.00 12.35 C ATOM 335 C PRO A 37 18.699 2.072 5.987 1.00 12.15 C ATOM 336 O PRO A 37 19.263 1.162 5.413 1.00 13.45 O ATOM 337 N PRO A 38 18.069 3.059 5.291 1.00 12.51 N ATOM 338 CA PRO A 38 17.526 4.340 5.802 1.00 11.81 C ATOM 339 CB PRO A 38 17.449 5.201 4.549 1.00 10.25 C ATOM 340 CG PRO A 38 17.147 4.182 3.365 1.00 9.40 C ATOM 341 CD PRO A 38 17.900 2.913 3.810 1.00 10.84 C ATOM 342 C PRO A 38 16.175 3.938 6.400 1.00 13.91 C ATOM 343 O PRO A 38 15.905 2.742 6.564 1.00 14.88 O ATOM 344 N LEU A 39 15.219 4.705 6.803 1.00 15.38 N ATOM 345 CA LEU A 39 14.063 3.608 7.197 1.00 15.49 C ATOM 346 CB LEU A 39 14.154 2.190 6.569 1.00 14.92 C ATOM 347 CG LEU A 39 12.971 1.265 5.976 1.00 18.58 C ATOM 348 CD1 LEU A 39 13.255 −0.195 5.671 1.00 19.59 C ATOM 349 CD2 LEU A 39 12.324 1.770 4.637 1.00 11.24 C ATOM 350 C LEU A 39 13.975 3.353 8.661 1.00 14.01 C ATOM 351 O LEU A 39 14.878 2.784 9.319 1.00 11.41 O ATOM 352 N THR A 40 12.827 3.808 9.110 1.00 14.12 N ATOM 353 CA THR A 40 12.557 4.170 10.483 1.00 15.41 C ATOM 354 CB THR A 40 12.758 5.677 10.653 1.00 16.77 C ATOM 355 OG1 THR A 40 11.901 6.359 9.732 1.00 15.44 O ATOM 356 CG2 THR A 40 14.229 6.045 10.340 1.00 11.31 C ATOM 357 C THR A 40 11.120 3.663 10.757 1.00 16.03 C ATOM 358 O THR A 40 10.531 3.951 11.780 1.00 17.93 O ATOM 359 N THR A 41 10.637 2.788 9.875 1.00 14.57 N ATOM 360 CA THR A 41 9.354 2.105 10.052 1.00 15.88 C ATOM 361 CB THR A 41 8.300 2.555 8.982 1.00 14.57 C ATOM 362 OG1 THR A 41 8.861 2.299 7.688 1.00 17.40 O ATOM 363 CG2 THR A 41 7.934 4.044 9.185 1.00 14.46 C ATOM 364 C THR A 41 9.575 0.583 10.018 1.00 15.83 C ATOM 365 O THR A 41 10.563 0.097 9.430 1.00 14.69 O ATOM 366 N GLY A 42 8.639 −0.152 10.613 1.00 16.94 N ATOM 367 CA GLY A 42 8.766 −1.596 10.828 1.00 18.20 C ATOM 368 C GLY A 42 7.644 −1.976 11.763 1.00 19.62 C ATOM 369 O GLY A 42 6.656 −1.278 11.839 1.00 20.86 O ATOM 370 N PRO A 43 7.770 −3.095 12.471 1.00 20.21 N ATOM 371 CA PRO A 43 6.810 −3.419 13.539 1.00 20.36 C ATOM 372 CB PRO A 43 7.399 −4.691 14.171 1.00 21.77 C ATOM 373 CG PRO A 43 8.766 −4.877 13.585 1.00 20.01 C ATOM 374 CD PRO A 43 8.835 −4.097 12.314 1.00 19.47 C ATOM 375 C PRO A 43 6.598 −2.319 14.631 1.00 19.46 C ATOM 376 O PRO A 43 7.561 −1.625 14.985 1.00 20.21 O ATOM 377 N PRO A 44 5.348 −2.153 15.133 1.00 19.30 N ATOM 378 CA PRO A 44 5.052 −1.157 16.164 1.00 19.49 C ATOM 379 CB PRO A 44 3.669 −1.559 16.689 1.00 19.77 C ATOM 380 CG PRO A 44 3.014 −2.130 15.453 1.00 19.90 C ATOM 381 CD PRO A 44 4.126 −2.906 14.744 1.00 18.39 C ATOM 382 C PRO A 44 6.136 −1.167 17.259 1.00 19.75 C ATOM 383 O PRO A 44 6.612 −0.113 17.698 1.00 19.34 O ATOM 384 N GLU A 45 6.611 −2.347 17.607 1.00 19.40 N ATOM 385 CA GLU A 45 7.605 −2.462 18.654 1.00 19.71 C ATOM 386 CB GLU A 45 7.680 −3.903 19.123 1.00 21.07 C ATOM 387 CG GLU A 45 8.633 −4.041 20.294 1.00 27.54 C ATOM 388 CD GLU A 45 8.408 −5.319 21.094 1.00 34.48 C ATOM 389 OE1 GLU A 45 7.879 −6.318 20.492 1.00 36.28 O ATOM 390 OE2 GLU A 45 8.768 −5.279 22.307 1.00 33.16 O ATOM 391 C GLU A 45 9.001 −1.915 18.283 1.00 18.56 C ATOM 392 O GLU A 45 9.719 −1.429 19.156 1.00 18.28 O ATOM 393 N PHE A 46 9.380 −1.963 16.995 1.00 16.03 N ATOM 394 CA PHE A 46 10.560 −1.264 16.602 1.00 15.23 C ATOM 395 CB PHE A 46 11.099 −1.721 15.239 1.00 14.81 C ATOM 396 CG PHE A 46 12.066 −0.764 14.700 1.00 17.22 C ATOM 397 CD1 PHE A 46 13.390 −0.756 15.153 1.00 14.12 C ATOM 398 CE1 PHE A 46 14.295 0.242 14.732 1.00 19.07 C ATOM 399 CZ PHE A 46 13.884 1.233 13.890 1.00 17.14 C ATOM 400 CE2 PHE A 46 12.537 1.232 13.428 1.00 17.68 C ATOM 401 CD2 PHE A 46 11.637 0.260 13.860 1.00 18.51 C ATOM 402 C PHE A 46 10.299 0.296 16.601 1.00 13.78 C ATOM 403 O PHE A 46 11.123 1.038 17.040 1.00 12.23 O ATOM 404 N GLU A 47 9.143 0.739 16.117 1.00 12.97 N ATOM 405 CA GLU A 47 8.795 2.144 15.986 1.00 11.61 C ATOM 406 CB GLU A 47 7.517 2.295 15.156 1.00 11.60 C ATOM 407 CG GLU A 47 7.725 1.795 13.706 1.00 10.58 C ATOM 408 CD GLU A 47 6.603 2.205 12.721 1.00 14.43 C ATOM 409 OE1 GLU A 47 5.642 2.946 13.076 1.00 16.62 O ATOM 410 OE2 GLU A 47 6.744 1.801 11.554 1.00 15.88 O ATOM 411 C GLU A 47 8.691 2.868 17.305 1.00 13.07 C ATOM 412 O GLU A 47 9.172 4.010 17.440 1.00 11.47 O ATOM 413 N ARG A 48 8.105 2.205 18.290 1.00 13.97 N ATOM 414 CA ARG A 48 8.188 2.722 19.665 1.00 15.04 C ATOM 415 CB ARG A 48 7.347 1.874 20.639 1.00 15.02 C ATOM 416 CG ARG A 48 5.844 1.967 20.364 1.00 14.43 C ATOM 417 CD ARG A 48 4.990 1.353 21.493 1.00 13.52 C ATOM 418 NE ARG A 48 5.592 0.097 21.947 1.00 13.44 N ATOM 419 CZ ARG A 48 5.269 −1.127 21.503 1.00 13.23 C ATOM 420 NH1 ARG A 48 4.309 −1.328 20.596 1.00 10.55 N ATOM 421 NH2 ARG A 48 5.929 −2.138 21.938 1.00 7.17 N ATOM 422 C ARG A 48 9.590 3.022 20.224 1.00 15.81 C ATOM 423 O ARG A 48 9.760 4.044 20.845 1.00 16.42 O ATOM 424 N VAL A 49 10.582 2.136 20.024 1.00 16.51 N ATOM 425 CA VAL A 49 11.923 2.367 20.523 1.00 14.75 C ATOM 426 CB VAL A 49 12.849 1.114 20.324 1.00 16.09 C ATOM 427 CG1 VAL A 49 14.301 1.370 20.855 1.00 14.60 C ATOM 428 CG2 VAL A 49 12.303 −0.088 21.055 1.00 16.72 C ATOM 429 C VAL A 49 12.553 3.508 19.743 1.00 14.72 C ATOM 430 O VAL A 49 13.198 4.372 20.338 1.00 12.53 O ATOM 431 N TYR A 50 12.468 3.449 18.406 1.00 12.52 N ATOM 432 CA TYR A 50 12.897 4.549 17.557 1.00 12.27 C ATOM 433 CB TYR A 50 12.485 4.247 16.125 1.00 13.15 C ATOM 434 CG TYR A 50 12.675 5.414 15.251 1.00 10.62 C ATOM 435 CD1 TYR A 50 13.959 5.777 14.880 1.00 12.53 C ATOM 436 CE1 TYR A 50 14.173 6.843 14.100 1.00 12.06 C ATOM 437 CZ TYR A 50 13.113 7.644 13.676 1.00 9.95 C ATOM 438 OH TYR A 50 13.469 8.739 12.908 1.00 11.26 O ATOM 439 CE2 TYR A 50 11.795 7.350 13.982 1.00 9.79 C ATOM 440 CD2 TYR A 50 11.581 6.177 14.801 1.00 13.35 C ATOM 441 C TYR A 50 12.312 5.904 18.006 1.00 12.31 C ATOM 442 O TYR A 50 13.030 6.911 18.241 1.00 13.28 O ATOM 443 N ARG A 51 11.001 5.928 18.188 1.00 12.34 N ATOM 444 CA ARG A 51 10.303 7.144 18.496 1.00 12.42 C ATOM 445 CB ARG A 51 8.795 6.869 18.371 1.00 14.04 C ATOM 446 CG ARG A 51 8.261 7.145 16.923 1.00 14.11 C ATOM 447 CD ARG A 51 7.721 8.577 17.058 1.00 23.55 C ATOM 448 NE ARG A 51 8.521 9.271 16.203 1.00 17.63 N ATOM 449 CZ ARG A 51 9.060 10.459 16.315 1.00 12.66 C ATOM 450 NH1 ARG A 51 8.852 11.367 17.275 1.00 13.62 N ATOM 451 NH2 ARG A 51 9.843 10.700 15.290 1.00 13.25 N ATOM 452 C ARG A 51 10.614 7.604 19.922 1.00 14.15 C ATOM 453 O ARG A 51 10.651 8.808 20.144 1.00 11.71 O ATOM 454 N ALA A 52 10.766 6.663 20.901 1.00 14.36 N ATOM 455 CA ALA A 52 11.112 7.066 22.267 1.00 13.96 C ATOM 456 CB ALA A 52 11.095 5.836 23.217 1.00 14.72 C ATOM 457 C ALA A 52 12.463 7.826 22.265 1.00 13.65 C ATOM 458 O ALA A 52 12.655 8.817 22.954 1.00 12.08 O ATOM 459 N GLN A 53 13.398 7.361 21.418 1.00 14.50 N ATOM 460 CA GLN A 53 14.706 7.937 21.347 1.00 13.04 C ATOM 461 CB GLN A 53 15.704 6.986 20.619 1.00 12.84 C ATOM 462 CG GLN A 53 17.113 7.675 20.304 1.00 12.80 C ATOM 463 CD GLN A 53 17.181 8.182 18.877 1.00 13.94 C ATOM 464 OE1 GLN A 53 17.004 7.424 17.939 1.00 16.24 O ATOM 465 NE2 GLN A 53 17.427 9.502 18.693 1.00 15.50 N ATOM 466 C GLN A 53 14.642 9.283 20.637 1.00 13.51 C ATOM 467 O GLN A 53 15.246 10.255 21.097 1.00 12.36 O ATOM 468 N VAL A 54 13.916 9.355 19.505 1.00 12.90 N ATOM 469 CA VAL A 54 13.851 10.610 18.783 1.00 10.80 C ATOM 470 CB VAL A 54 13.092 10.425 17.479 1.00 11.95 C ATOM 471 CG1 VAL A 54 12.779 11.766 16.825 1.00 7.46 C ATOM 472 CG2 VAL A 54 13.891 9.504 16.524 1.00 9.26 C ATOM 473 C VAL A 54 13.176 11.675 19.671 1.00 11.94 C ATOM 474 O VAL A 54 13.554 12.809 19.642 1.00 12.72 O ATOM 475 N ASN A 55 12.156 11.297 20.443 1.00 11.98 N ATOM 476 CA ASN A 55 11.465 12.261 21.301 1.00 12.46 C ATOM 477 CB ASN A 55 10.179 11.650 21.950 1.00 9.74 C ATOM 478 CG ASN A 55 9.332 12.678 22.694 1.00 13.90 C ATOM 479 OD1 ASN A 55 9.691 13.107 23.815 1.00 15.04 O ATOM 480 ND2 ASN A 55 8.231 13.151 22.050 1.00 6.77 N ATOM 481 C ASN A 55 12.403 12.810 22.353 1.00 11.37 C ATOM 482 O ASN A 55 12.440 14.025 22.586 1.00 11.95 O ATOM 483 N CYS A 56 13.137 11.906 23.022 1.00 11.84 N ATOM 484 CA CYS A 56 14.116 12.344 24.024 1.00 12.82 C ATOM 485 CB CYS A 56 14.794 11.145 24.729 1.00 11.54 C ATOM 486 SG CYS A 56 13.622 10.159 25.693 1.00 18.21 S ATOM 487 C CYS A 56 15.150 13.273 23.368 1.00 11.89 C ATOM 488 O CYS A 56 15.511 14.275 23.950 1.00 9.84 O ATOM 489 N SER A 57 15.634 12.918 22.172 1.00 12.11 N ATOM 490 CA SER A 57 16.655 13.730 21.479 1.00 13.22 C ATOM 491 CB SER A 57 17.141 13.114 20.150 1.00 13.25 C ATOM 492 OG SER A 57 17.733 11.872 20.383 1.00 17.22 O ATOM 493 C SER A 57 16.088 15.106 21.137 1.00 14.26 C ATOM 494 O SER A 57 16.810 16.074 21.196 1.00 12.95 O ATOM 495 N GLU A 58 14.813 15.207 20.733 1.00 15.19 N ATOM 496 CA GLU A 58 14.374 16.567 20.393 1.00 15.85 C ATOM 497 CB GLU A 58 13.209 16.584 19.423 1.00 18.23 C ATOM 498 CG GLU A 58 11.967 16.232 20.029 1.00 19.53 C ATOM 499 CD GLU A 58 10.859 15.915 18.951 1.00 24.35 C ATOM 500 OE1 GLU A 58 11.115 16.019 17.730 1.00 22.29 O ATOM 501 OE2 GLU A 58 9.771 15.494 19.374 1.00 19.32 O ATOM 502 C GLU A 58 14.124 17.480 21.575 1.00 15.55 C ATOM 503 O GLU A 58 14.276 18.702 21.414 1.00 13.27 O ATOM 504 N TYR A 59 13.818 16.912 22.762 1.00 13.72 N ATOM 505 CA TYR A 59 13.730 17.730 23.973 1.00 13.56 C ATOM 506 CB TYR A 59 12.756 17.146 25.011 1.00 14.18 C ATOM 507 CG TYR A 59 11.268 17.317 24.653 1.00 15.13 C ATOM 508 CD1 TYR A 59 10.517 18.401 25.180 1.00 16.03 C ATOM 509 CE1 TYR A 59 9.142 18.585 24.842 1.00 15.15 C ATOM 510 CZ TYR A 59 8.536 17.605 24.039 1.00 15.61 C ATOM 511 OH TYR A 59 7.218 17.734 23.715 1.00 15.78 O ATOM 512 CE2 TYR A 59 9.278 16.585 23.470 1.00 11.76 C ATOM 513 CD2 TYR A 59 10.620 16.427 23.781 1.00 12.40 C ATOM 514 C TYR A 59 15.062 17.965 24.656 1.00 13.24 C ATOM 515 O TYR A 59 15.168 18.830 25.518 1.00 11.08 O ATOM 516 N PHE A 60 16.064 17.161 24.322 1.00 13.07 N ATOM 517 CA PHE A 60 17.376 17.305 24.919 1.00 13.02 C ATOM 518 CB PHE A 60 18.365 16.191 24.437 1.00 13.22 C ATOM 519 CG PHE A 60 19.663 16.094 25.237 1.00 11.22 C ATOM 520 CD1 PHE A 60 19.651 15.779 26.614 1.00 17.34 C ATOM 521 CE1 PHE A 60 20.828 15.682 27.352 1.00 12.55 C ATOM 522 CZ PHE A 60 22.034 15.892 26.714 1.00 12.20 C ATOM 523 CE2 PHE A 60 22.090 16.245 25.410 1.00 14.53 C ATOM 524 CD2 PHE A 60 20.866 16.303 24.630 1.00 13.00 C ATOM 525 C PHE A 60 17.985 18.741 24.907 1.00 13.07 C ATOM 526 O PHE A 60 18.493 19.159 25.922 1.00 13.53 O ATOM 527 N PRO A 61 18.016 19.461 23.745 1.00 14.18 N ATOM 528 CA PRO A 61 18.541 20.831 23.851 1.00 13.05 C ATOM 529 CB PRO A 61 18.561 21.353 22.380 1.00 12.70 C ATOM 530 CG PRO A 61 18.455 20.061 21.536 1.00 12.61 C ATOM 531 CD PRO A 61 17.683 19.070 22.339 1.00 10.04 C ATOM 532 C PRO A 61 17.685 21.789 24.685 1.00 14.93 C ATOM 533 O PRO A 61 18.217 22.775 25.147 1.00 14.83 O ATOM 534 N LEU A 62 16.366 21.542 24.812 1.00 15.61 N ATOM 535 CA LEU A 62 15.537 22.402 25.615 1.00 15.15 C ATOM 536 CB LEU A 62 14.084 22.004 25.437 1.00 15.98 C ATOM 537 CG LEU A 62 13.346 22.529 24.238 1.00 18.01 C ATOM 538 CD1 LEU A 62 14.129 22.750 22.948 1.00 19.31 C ATOM 539 CD2 LEU A 62 12.063 21.759 24.065 1.00 20.44 C ATOM 540 C LEU A 62 15.960 22.178 27.052 1.00 15.52 C ATOM 541 O LEU A 62 16.059 23.105 27.849 1.00 13.51 O ATOM 542 N PHE A 63 16.183 20.916 27.413 1.00 13.75 N ATOM 543 CA PHE A 63 16.612 20.651 28.733 1.00 14.28 C ATOM 544 CB PHE A 63 16.639 19.132 28.947 1.00 14.43 C ATOM 545 CG PHE A 63 17.597 18.678 30.045 1.00 18.25 C ATOM 546 CD1 PHE A 63 17.305 18.899 31.394 1.00 19.16 C ATOM 547 CE1 PHE A 63 18.201 18.419 32.424 1.00 17.16 C ATOM 548 CZ PHE A 63 19.352 17.753 32.057 1.00 15.03 C ATOM 549 CE2 PHE A 63 19.674 17.571 30.735 1.00 22.75 C ATOM 550 CD2 PHE A 63 18.775 18.003 29.710 1.00 17.50 C ATOM 551 C PHE A 63 17.982 21.334 29.046 1.00 14.58 C ATOM 552 O PHE A 63 18.143 21.911 30.093 1.00 14.07 O ATOM 553 N LEU A 64 18.983 21.165 28.181 1.00 14.45 N ATOM 554 CA LEU A 64 20.322 21.755 28.402 1.00 15.20 C ATOM 555 CB LEU A 64 21.284 21.419 27.246 1.00 15.87 C ATOM 556 CG LEU A 64 21.739 19.946 27.212 1.00 22.75 C ATOM 557 CD1 LEU A 64 22.914 19.754 26.320 1.00 27.77 C ATOM 558 CD2 LEU A 64 22.123 19.428 28.622 1.00 22.63 C ATOM 559 C LEU A 64 20.222 23.255 28.525 1.00 13.47 C ATOM 560 O LEU A 64 20.840 23.833 29.401 1.00 14.28 O ATOM 561 N ALA A 65 19.477 23.884 27.630 1.00 12.85 N ATOM 562 CA ALA A 65 19.400 25.358 27.619 1.00 13.24 C ATOM 563 CB ALA A 65 18.501 25.842 26.473 1.00 10.80 C ATOM 564 C ALA A 65 18.867 25.866 28.935 1.00 13.87 C ATOM 565 O ALA A 65 19.429 26.822 29.568 1.00 12.95 O ATOM 566 N THR A 66 17.780 25.212 29.360 1.00 12.63 N ATOM 567 CA ATHR A 66 17.011 25.635 30.507 0.50 13.55 C ATOM 568 CA BTHR A 66 17.089 25.720 30.525 0.50 13.85 C ATOM 569 CB ATHR A 66 15.614 24.923 30.414 0.50 12.60 C ATOM 570 CB BTHR A 66 15.597 25.358 30.552 0.50 13.34 C ATOM 571 OG1 ATHR A 66 14.877 25.415 29.278 0.50 8.39 O ATOM 572 OG1 BTHR A 66 14.995 26.151 31.573 0.50 15.39 O ATOM 573 CG2 ATHR A 66 14.823 25.160 31.625 0.50 14.87 C ATOM 574 CG2 BTHR A 66 15.390 23.907 30.905 0.50 10.32 C ATOM 575 C THR A 66 17.785 25.363 31.852 1.00 14.13 C ATOM 576 O THR A 66 17.830 26.178 32.763 1.00 14.63 O ATOM 577 N LEU A 67 18.372 24.179 31.939 1.00 14.49 N ATOM 578 CA LEU A 67 19.321 23.795 33.002 1.00 12.69 C ATOM 579 CB LEU A 67 19.996 22.449 32.629 1.00 13.54 C ATOM 580 CG LEU A 67 21.083 21.928 33.570 1.00 8.83 C ATOM 581 CD1 LEU A 67 20.388 21.495 34.959 1.00 7.51 C ATOM 582 CD2 LEU A 67 21.921 20.772 32.962 1.00 12.44 C ATOM 583 C LEU A 67 20.391 24.883 33.263 1.00 14.47 C ATOM 584 O LEU A 67 20.612 25.276 34.428 1.00 13.40 O ATOM 585 N TRP A 68 21.090 25.295 32.203 1.00 12.00 N ATOM 586 CA TRP A 68 22.181 26.233 32.303 1.00 13.04 C ATOM 587 CB TRP A 68 23.044 26.221 31.005 1.00 10.77 C ATOM 588 CG TRP A 68 23.990 25.029 31.064 1.00 13.93 C ATOM 589 CD1 TRP A 68 23.748 23.718 30.618 1.00 12.43 C ATOM 590 NE1 TRP A 68 24.832 22.926 30.908 1.00 9.53 N ATOM 591 CE2 TRP A 68 25.808 23.698 31.500 1.00 12.27 C ATOM 592 CD2 TRP A 68 25.309 25.016 31.630 1.00 11.94 C ATOM 593 CE3 TRP A 68 26.126 26.006 32.229 1.00 16.53 C ATOM 594 CZ3 TRP A 68 27.362 25.658 32.651 1.00 15.09 C ATOM 595 CH2 TRP A 68 27.847 24.291 32.521 1.00 11.03 C ATOM 596 CZ2 TRP A 68 27.082 23.334 31.954 1.00 11.78 C ATOM 597 C TRP A 68 21.678 27.629 32.676 1.00 12.25 C ATOM 598 O TRP A 68 22.271 28.259 33.527 1.00 12.94 O ATOM 599 N VAL A 69 20.585 28.087 32.052 1.00 11.26 N ATOM 600 CA VAL A 69 20.049 29.385 32.383 1.00 10.51 C ATOM 601 CB VAL A 69 18.965 29.886 31.365 1.00 10.37 C ATOM 602 CG1 VAL A 69 18.396 31.246 31.893 1.00 7.69 C ATOM 603 CG2 VAL A 69 19.635 30.133 29.934 1.00 9.36 C ATOM 604 C VAL A 69 19.513 29.373 33.820 1.00 11.73 C ATOM 605 O VAL A 69 19.782 30.272 34.550 1.00 11.65 O ATOM 606 N ALA A 70 18.744 28.347 34.227 1.00 11.50 N ATOM 607 CA ALA A 70 18.267 28.297 35.620 1.00 11.42 C ATOM 608 CB ALA A 70 17.266 27.106 35.883 1.00 10.19 C ATOM 609 C ALA A 70 19.443 28.184 36.596 1.00 12.67 C ATOM 610 O ALA A 70 19.405 28.803 37.682 1.00 11.04 O ATOM 611 N GLY A 71 20.440 27.364 36.258 1.00 12.51 N ATOM 612 CA GLY A 71 21.555 27.166 37.157 1.00 13.85 C ATOM 613 C GLY A 71 22.394 28.419 37.321 1.00 14.72 C ATOM 614 O GLY A 71 22.945 28.625 38.359 1.00 15.04 O ATOM 615 N ILE A 72 22.547 29.224 36.284 1.00 15.76 N ATOM 616 CA ILE A 72 23.340 30.476 36.402 1.00 15.94 C ATOM 617 CB ILE A 72 23.940 30.843 35.025 1.00 17.01 C ATOM 618 CG1 ILE A 72 25.052 29.829 34.772 1.00 20.65 C ATOM 619 CD1 ILE A 72 25.365 29.700 33.330 1.00 25.78 C ATOM 620 CG2 ILE A 72 24.568 32.263 35.001 1.00 15.51 C ATOM 621 C ILE A 72 22.594 31.656 37.060 1.00 16.58 C ATOM 622 O ILE A 72 23.148 32.394 37.845 1.00 17.07 O ATOM 623 N PHE A 73 21.304 31.798 36.753 1.00 16.25 N ATOM 624 CA PHE A 73 20.539 32.993 37.092 1.00 13.94 C ATOM 625 CB PHE A 73 19.718 33.521 35.865 1.00 12.32 C ATOM 626 CG PHE A 73 20.570 34.265 34.861 1.00 15.58 C ATOM 627 CD1 PHE A 73 20.818 35.669 34.997 1.00 13.34 C ATOM 628 CE1 PHE A 73 21.671 36.343 34.056 1.00 14.64 C ATOM 629 CZ PHE A 73 22.312 35.551 33.034 1.00 10.84 C ATOM 630 CE2 PHE A 73 22.033 34.161 32.972 1.00 13.67 C ATOM 631 CD2 PHE A 73 21.209 33.557 33.842 1.00 12.49 C ATOM 632 C PHE A 73 19.695 32.702 38.323 1.00 13.02 C ATOM 633 O PHE A 73 19.265 33.650 39.004 1.00 12.63 O ATOM 634 N PHE A 74 19.458 31.442 38.659 1.00 10.90 N ATOM 635 CA PHE A 74 18.542 31.234 39.809 1.00 11.36 C ATOM 636 CB PHE A 74 17.222 30.468 39.467 1.00 11.30 C ATOM 637 CG PHE A 74 16.323 30.260 40.693 1.00 11.70 C ATOM 638 CD1 PHE A 74 15.372 31.209 41.062 1.00 10.85 C ATOM 639 CE1 PHE A 74 14.543 31.064 42.226 1.00 12.62 C ATOM 640 CZ PHE A 74 14.753 30.010 43.087 1.00 11.26 C ATOM 641 CE2 PHE A 74 15.719 29.035 42.746 1.00 15.01 C ATOM 642 CD2 PHE A 74 16.509 29.179 41.535 1.00 16.36 C ATOM 643 C PHE A 74 19.325 30.583 40.967 1.00 13.78 C ATOM 644 O PHE A 74 19.557 31.229 41.991 1.00 13.01 O ATOM 645 N HIS A 75 19.806 29.341 40.806 1.00 13.91 N ATOM 646 CA HIS A 75 20.512 28.633 41.902 1.00 13.91 C ATOM 647 CB HIS A 75 19.539 28.274 43.039 1.00 13.67 C ATOM 648 CG HIS A 75 20.189 27.633 44.229 1.00 12.20 C ATOM 649 ND1 HIS A 75 20.328 26.273 44.346 1.00 11.93 N ATOM 650 CE1 HIS A 75 20.913 25.981 45.493 1.00 13.03 C ATOM 651 NE2 HIS A 75 21.173 27.114 46.125 1.00 10.22 N ATOM 652 CD2 HIS A 75 20.704 28.162 45.369 1.00 10.73 C ATOM 653 C HIS A 75 21.003 27.332 41.272 1.00 14.40 C ATOM 654 O HIS A 75 20.201 26.578 40.723 1.00 14.22 O ATOM 655 N GLU A 76 22.298 27.058 41.383 1.00 13.47 N ATOM 656 CA GLU A 76 22.903 25.862 40.777 1.00 15.28 C ATOM 657 CB GLU A 76 24.467 25.933 40.797 1.00 13.94 C ATOM 658 CG GLU A 76 25.036 24.964 39.771 1.00 16.66 C ATOM 659 CD GLU A 76 26.464 24.478 40.055 1.00 19.99 C ATOM 660 OE1 GLU A 76 27.005 24.723 41.125 1.00 23.00 O ATOM 661 OE2 GLU A 76 27.078 23.817 39.202 1.00 20.47 O ATOM 662 C GLU A 76 22.398 24.522 41.294 1.00 14.98 C ATOM 663 O GLU A 76 22.126 23.669 40.492 1.00 17.45 O ATOM 664 N GLY A 77 22.300 24.309 42.614 1.00 14.20 N ATOM 665 CA GLY A 77 21.830 23.076 43.192 1.00 12.60 C ATOM 666 C GLY A 77 20.403 22.759 42.849 1.00 14.63 C ATOM 667 O GLY A 77 20.048 21.592 42.545 1.00 13.52 O ATOM 668 N ALA A 78 19.539 23.768 42.898 1.00 14.71 N ATOM 669 CA ALA A 78 18.139 23.580 42.513 1.00 13.75 C ATOM 670 CB ALA A 78 17.294 24.901 42.768 1.00 13.00 C ATOM 671 C ALA A 78 17.986 23.131 41.089 1.00 13.82 C ATOM 672 O ALA A 78 17.144 22.201 40.763 1.00 14.20 O ATOM 673 N ALA A 79 18.743 23.781 40.204 1.00 14.04 N ATOM 674 CA ALA A 79 18.618 23.502 38.775 1.00 12.36 C ATOM 675 CB ALA A 79 19.402 24.496 37.934 1.00 9.24 C ATOM 676 C ALA A 79 19.112 22.081 38.495 1.00 13.04 C ATOM 677 O ALA A 79 18.448 21.302 37.774 1.00 13.24 O ATOM 678 N ALA A 80 20.260 21.735 39.093 1.00 13.27 N ATOM 679 CA ALA A 80 20.877 20.407 38.954 1.00 11.95 C ATOM 680 CB ALA A 80 22.173 20.315 39.729 1.00 10.13 C ATOM 681 C ALA A 80 19.932 19.320 39.445 1.00 13.89 C ATOM 682 O ALA A 80 19.749 18.306 38.774 1.00 13.84 O ATOM 683 N LEU A 81 19.306 19.564 40.587 1.00 14.77 N ATOM 684 CA LEU A 81 18.326 18.657 41.154 1.00 16.92 C ATOM 685 CB LEU A 81 17.851 19.276 42.444 1.00 17.72 C ATOM 686 CG LEU A 81 17.596 18.454 43.677 1.00 26.70 C ATOM 687 CD1 LEU A 81 18.461 17.115 43.668 1.00 30.82 C ATOM 688 CD2 LEU A 81 17.947 19.438 44.895 1.00 31.30 C ATOM 689 C LEU A 81 17.090 18.465 40.237 1.00 15.28 C ATOM 690 O LEU A 81 16.691 17.354 40.014 1.00 13.83 O ATOM 691 N CYS A 82 16.448 19.550 39.774 1.00 15.11 N ATOM 692 CA CYS A 82 15.398 19.411 38.722 1.00 16.94 C ATOM 693 CB CYS A 82 14.737 20.724 38.254 1.00 16.28 C ATOM 694 SG CYS A 82 14.157 21.763 39.515 1.00 23.74 S ATOM 695 C CYS A 82 15.873 18.668 37.480 1.00 16.03 C ATOM 696 O CYS A 82 15.072 17.958 36.840 1.00 16.87 O ATOM 697 N GLY A 83 17.133 18.922 37.105 1.00 16.23 N ATOM 698 CA GLY A 83 17.811 18.200 36.056 1.00 14.48 C ATOM 699 C GLY A 83 17.856 16.677 36.180 1.00 14.60 C ATOM 700 O GLY A 83 17.528 15.959 35.215 1.00 13.92 O ATOM 701 N LEU A 84 18.246 16.177 37.359 1.00 14.89 N ATOM 702 CA LEU A 84 18.247 14.778 37.632 1.00 15.09 C ATOM 703 CB LEU A 84 18.742 14.472 39.034 1.00 16.29 C ATOM 704 CG LEU A 84 20.232 14.789 39.235 1.00 17.97 C ATOM 705 CD1 LEU A 84 20.546 14.556 40.725 1.00 20.25 C ATOM 706 CD2 LEU A 84 21.082 13.828 38.252 1.00 18.58 C ATOM 707 C LEU A 84 16.867 14.225 37.577 1.00 14.51 C ATOM 708 O LEU A 84 16.672 13.152 37.000 1.00 13.34 O ATOM 709 N VAL A 85 15.933 14.918 38.208 1.00 12.53 N ATOM 710 CA VAL A 85 14.516 14.476 38.156 1.00 13.74 C ATOM 711 CB VAL A 85 13.536 15.399 39.001 1.00 13.07 C ATOM 712 CG1 VAL A 85 12.020 15.035 38.687 1.00 15.53 C ATOM 713 CG2 VAL A 85 13.866 15.270 40.449 1.00 14.98 C ATOM 714 C VAL A 85 13.991 14.357 36.692 1.00 12.69 C ATOM 715 O VAL A 85 13.370 13.360 36.371 1.00 11.34 O ATOM 716 N TYR A 86 14.279 15.363 35.839 1.00 11.34 N ATOM 717 CA TYR A 86 13.941 15.315 34.419 1.00 11.49 C ATOM 718 CB TYR A 86 14.351 16.657 33.721 1.00 10.90 C ATOM 719 CG TYR A 86 14.211 16.591 32.237 1.00 11.85 C ATOM 720 CD1 TYR A 86 12.977 16.837 31.634 1.00 11.77 C ATOM 721 CE1 TYR A 86 12.822 16.718 30.228 1.00 12.10 C ATOM 722 CZ TYR A 86 13.885 16.330 29.484 1.00 14.05 C ATOM 723 OH TYR A 86 13.726 16.166 28.114 1.00 14.10 O ATOM 724 CE2 TYR A 86 15.107 16.003 30.089 1.00 13.31 C ATOM 725 CD2 TYR A 86 15.266 16.116 31.436 1.00 7.03 C ATOM 726 C TYR A 86 14.592 14.107 33.733 1.00 12.33 C ATOM 727 O TYR A 86 13.939 13.382 32.993 1.00 13.31 O ATOM 728 N LEU A 87 15.882 13.859 33.979 1.00 13.85 N ATOM 729 CA LEU A 87 16.568 12.763 33.317 1.00 13.13 C ATOM 730 CB LEU A 87 18.103 12.881 33.500 1.00 14.25 C ATOM 731 CG LEU A 87 18.784 14.080 32.824 1.00 13.79 C ATOM 732 CD1 LEU A 87 20.269 14.022 33.173 1.00 10.18 C ATOM 733 CD2 LEU A 87 18.543 13.997 31.274 1.00 8.93 C ATOM 734 C LEU A 87 16.080 11.363 33.762 1.00 13.61 C ATOM 735 O LEU A 87 15.955 10.441 32.943 1.00 12.97 O ATOM 736 N PHE A 88 15.801 11.216 35.052 1.00 12.37 N ATOM 737 CA PHE A 88 15.252 10.022 35.518 1.00 13.75 C ATOM 738 CB PHE A 88 15.275 9.996 37.049 1.00 15.47 C ATOM 739 CG PHE A 88 14.693 8.736 37.611 1.00 21.57 C ATOM 740 CD1 PHE A 88 15.121 7.488 37.145 1.00 29.43 C ATOM 741 CE1 PHE A 88 14.558 6.304 37.655 1.00 31.14 C ATOM 742 CZ PHE A 88 13.568 6.367 38.664 1.00 28.33 C ATOM 743 CE2 PHE A 88 13.146 7.597 39.131 1.00 30.00 C ATOM 744 CD2 PHE A 88 13.682 8.773 38.580 1.00 27.56 C ATOM 745 C PHE A 88 13.839 9.782 34.943 1.00 12.86 C ATOM 746 O PHE A 88 13.523 8.684 34.608 1.00 12.67 O ATOM 747 N ALA A 89 13.001 10.814 34.845 1.00 13.33 N ATOM 748 CA ALA A 89 11.741 10.695 34.191 1.00 14.62 C ATOM 749 CB ALA A 89 10.903 12.040 34.308 1.00 12.92 C ATOM 750 C ALA A 89 11.903 10.316 32.702 1.00 14.55 C ATOM 751 O ALA A 89 11.016 9.643 32.169 1.00 16.54 O ATOM 752 N ARG A 90 12.951 10.820 32.015 1.00 14.18 N ATOM 753 CA ARG A 90 13.209 10.490 30.581 1.00 14.57 C ATOM 754 CB ARG A 90 14.205 11.435 29.923 1.00 14.34 C ATOM 755 CG ARG A 90 13.597 12.752 29.498 1.00 19.24 C ATOM 756 CD ARG A 90 12.678 12.414 28.351 1.00 24.50 C ATOM 757 NE ARG A 90 11.899 13.519 27.802 1.00 24.92 N ATOM 758 CZ ARG A 90 11.128 13.469 26.705 1.00 23.57 C ATOM 759 NH1 ARG A 90 11.019 12.380 25.951 1.00 18.81 N ATOM 760 NH2 ARG A 90 10.432 14.527 26.354 1.00 23.30 N ATOM 761 C ARG A 90 13.599 9.013 30.390 1.00 12.53 C ATOM 762 O ARG A 90 13.096 8.382 29.473 1.00 13.13 O ATOM 763 N LEU A 91 14.397 8.451 31.299 1.00 14.15 N ATOM 764 CA LEU A 91 14.721 7.011 31.322 1.00 13.85 C ATOM 765 CB LEU A 91 15.567 6.688 32.558 1.00 16.27 C ATOM 766 CG LEU A 91 16.522 5.488 32.568 1.00 17.38 C ATOM 767 CD1 LEU A 91 16.961 4.874 33.956 1.00 14.17 C ATOM 768 CD2 LEU A 91 16.258 4.538 31.433 1.00 13.85 C ATOM 769 C LEU A 91 13.393 6.232 31.422 1.00 13.93 C ATOM 770 O LEU A 91 13.171 5.310 30.670 1.00 12.31 O ATOM 771 N ARG A 92 12.527 6.602 32.394 1.00 13.99 N ATOM 772 CA ARG A 92 11.224 5.918 32.592 1.00 14.17 C ATOM 773 CB ARG A 92 10.455 6.385 33.832 1.00 11.97 C ATOM 774 CG ARG A 92 11.188 6.019 35.131 1.00 15.16 C ATOM 775 CD ARG A 92 10.294 6.149 36.413 1.00 19.31 C ATOM 776 NE ARG A 92 9.417 7.356 36.441 1.00 31.40 N ATOM 777 CZ ARG A 92 9.736 8.616 36.839 1.00 33.81 C ATOM 778 NH1 ARG A 92 10.963 8.960 37.316 1.00 30.93 N ATOM 779 NH2 ARG A 92 8.771 9.547 36.787 1.00 33.74 N ATOM 780 C ARG A 92 10.360 6.086 31.350 1.00 14.55 C ATOM 781 O ARG A 92 9.654 5.153 30.999 1.00 13.96 O ATOM 782 N TYR A 93 10.450 7.243 30.669 1.00 14.13 N ATOM 783 CA TYR A 93 9.653 7.465 29.440 1.00 13.44 C ATOM 784 CB TYR A 93 9.700 8.948 29.034 1.00 13.24 C ATOM 785 CG TYR A 93 9.181 9.284 27.632 1.00 11.08 C ATOM 786 CD1 TYR A 93 7.854 9.650 27.433 1.00 9.64 C ATOM 787 CE1 TYR A 93 7.381 10.010 26.158 1.00 7.71 C ATOM 788 CZ TYR A 93 8.223 9.909 25.055 1.00 9.98 C ATOM 789 OH TYR A 93 7.720 10.213 23.847 1.00 12.50 O ATOM 790 CE2 TYR A 93 9.534 9.496 25.163 1.00 8.83 C ATOM 791 CD2 TYR A 93 10.021 9.185 26.505 1.00 9.40 C ATOM 792 C TYR A 93 10.056 6.511 28.328 1.00 14.35 C ATOM 793 O TYR A 93 9.205 5.836 27.684 1.00 12.63 O ATOM 794 N PHE A 94 11.374 6.416 28.152 1.00 13.74 N ATOM 795 CA PHE A 94 11.932 5.588 27.161 1.00 13.21 C ATOM 796 CB PHE A 94 13.442 5.809 27.057 1.00 13.53 C ATOM 797 CG PHE A 94 14.078 4.939 26.031 1.00 14.20 C ATOM 798 CD1 PHE A 94 14.260 5.418 24.711 1.00 15.87 C ATOM 799 CE1 PHE A 94 14.840 4.569 23.706 1.00 15.83 C ATOM 800 CZ PHE A 94 15.205 3.258 24.062 1.00 14.61 C ATOM 801 CE2 PHE A 94 15.065 2.795 25.382 1.00 14.02 C ATOM 802 CD2 PHE A 94 14.478 3.634 26.358 1.00 13.17 C ATOM 803 C PHE A 94 11.609 4.111 27.407 1.00 14.91 C ATOM 804 O PHE A 94 11.120 3.418 26.468 1.00 12.70 O ATOM 805 N GLN A 95 11.872 3.630 28.639 1.00 14.32 N ATOM 806 CA GLN A 95 11.529 2.241 29.005 1.00 16.12 C ATOM 807 CB GLN A 95 11.958 1.928 30.442 1.00 14.85 C ATOM 808 CG GLN A 95 13.515 2.021 30.619 1.00 20.59 C ATOM 809 CD GLN A 95 13.962 1.866 32.106 1.00 21.10 C ATOM 810 OE1 GLN A 95 13.324 2.408 33.060 1.00 26.27 O ATOM 811 NE2 GLN A 95 15.066 1.122 32.308 1.00 26.90 N ATOM 812 C GLN A 95 10.018 1.907 28.844 1.00 15.85 C ATOM 813 O GLN A 95 9.665 0.796 28.412 1.00 17.07 O ATOM 814 N GLY A 96 9.143 2.829 29.253 1.00 14.21 N ATOM 815 CA GLY A 96 7.705 2.678 29.142 1.00 14.91 C ATOM 816 C GLY A 96 7.181 2.653 27.705 1.00 14.07 C ATOM 817 O GLY A 96 6.546 1.698 27.323 1.00 15.31 O ATOM 818 N TYR A 97 7.453 3.708 26.946 1.00 14.51 N ATOM 819 CA TYR A 97 7.156 3.837 25.515 1.00 14.17 C ATOM 820 CB TYR A 97 7.808 5.115 24.960 1.00 13.01 C ATOM 821 CG TYR A 97 7.242 5.618 23.664 1.00 12.30 C ATOM 822 CD1 TYR A 97 6.292 4.857 22.919 1.00 13.51 C ATOM 823 CE1 TYR A 97 5.750 5.377 21.710 1.00 11.95 C ATOM 824 CZ TYR A 97 6.256 6.590 21.200 1.00 9.43 C ATOM 825 OH TYR A 97 5.790 7.153 20.039 1.00 10.23 O ATOM 826 CE2 TYR A 97 7.177 7.350 21.930 1.00 11.59 C ATOM 827 CD2 TYR A 97 7.675 6.844 23.142 1.00 15.09 C ATOM 828 C TYR A 97 7.624 2.557 24.780 1.00 15.40 C ATOM 829 O TYR A 97 6.858 1.983 24.054 1.00 13.84 O ATOM 830 N ALA A 98 8.830 2.044 25.069 1.00 15.47 N ATOM 831 CA ALA A 98 9.261 0.782 24.447 1.00 15.13 C ATOM 832 CB ALA A 98 10.685 0.411 24.828 1.00 14.78 C ATOM 833 C ALA A 98 8.294 −0.390 24.683 1.00 15.60 C ATOM 834 O ALA A 98 8.005 −1.120 23.757 1.00 15.78 O ATOM 835 N ARG A 99 7.782 −0.544 25.888 1.00 14.89 N ATOM 836 CA ARG A 99 6.758 −1.550 26.186 1.00 18.61 C ATOM 837 CB ARG A 99 6.544 −1.754 27.710 1.00 17.12 C ATOM 838 CG ARG A 99 7.711 −2.393 28.353 1.00 22.91 C ATOM 839 CD ARG A 99 7.615 −2.367 29.913 1.00 26.13 C ATOM 840 NE ARG A 99 6.527 −3.239 30.478 1.00 31.86 N ATOM 841 CZ ARG A 99 5.962 −3.001 31.691 1.00 36.64 C ATOM 842 NH1 ARG A 99 6.377 −1.933 32.430 1.00 36.40 N ATOM 843 NH2 ARG A 99 4.983 −3.793 32.183 1.00 35.37 N ATOM 844 C ARG A 99 5.395 −1.259 25.586 1.00 16.35 C ATOM 845 O ARG A 99 4.706 −2.178 25.184 1.00 18.90 O ATOM 846 N SER A 100 4.994 −0.004 25.582 1.00 14.50 N ATOM 847 CA SER A 100 3.634 0.330 25.256 1.00 15.14 C ATOM 848 CB SER A 100 2.827 −0.085 26.473 1.00 14.49 C ATOM 849 OG SER A 100 1.516 0.163 26.252 1.00 14.92 O ATOM 850 C SER A 100 3.514 1.857 25.011 1.00 15.28 C ATOM 851 O SER A 100 4.074 2.660 25.765 1.00 15.11 O ATOM 852 N ALA A 101 2.790 2.275 23.976 1.00 16.34 N ATOM 853 CA ALA A 101 2.545 3.706 23.806 1.00 16.79 C ATOM 854 CB ALA A 101 1.726 3.988 22.569 1.00 17.05 C ATOM 855 C ALA A 101 1.878 4.293 25.066 1.00 17.22 C ATOM 856 O ALA A 101 2.270 5.358 25.535 1.00 18.57 O ATOM 857 N GLN A 102 0.925 3.583 25.652 1.00 15.32 N ATOM 858 CA GLN A 102 0.214 4.095 26.836 1.00 15.90 C ATOM 859 CB GLN A 102 −1.049 3.224 27.162 1.00 14.84 C ATOM 860 CG GLN A 102 −1.968 3.823 28.277 1.00 13.81 C ATOM 861 CD GLN A 102 −1.476 3.444 29.699 1.00 17.70 C ATOM 862 OE1 GLN A 102 −0.779 2.433 29.897 1.00 19.22 O ATOM 863 NE2 GLN A 102 −1.861 4.222 30.674 1.00 17.49 N ATOM 864 C GLN A 102 1.169 4.293 28.057 1.00 16.02 C ATOM 865 O GLN A 102 1.001 5.238 28.792 1.00 17.70 O ATOM 866 N LEU A 103 2.206 3.452 28.200 1.00 15.32 N ATOM 867 CA LEU A 103 3.155 3.553 29.292 1.00 15.42 C ATOM 868 CB LEU A 103 3.926 2.251 29.531 1.00 13.30 C ATOM 869 CG LEU A 103 3.111 1.164 30.209 1.00 16.00 C ATOM 870 CD1 LEU A 103 3.808 −0.159 29.972 1.00 17.16 C ATOM 871 CD2 LEU A 103 2.796 1.400 31.705 1.00 8.03 C ATOM 872 C LEU A 103 4.142 4.698 29.166 1.00 15.78 C ATOM 873 O LEU A 103 4.889 4.946 30.094 1.00 17.02 O ATOM 874 N ARG A 104 4.172 5.390 28.034 1.00 16.09 N ATOM 875 CA ARG A 104 4.968 6.627 27.928 1.00 14.49 C ATOM 876 CB ARG A 104 5.161 7.073 26.470 1.00 15.67 C ATOM 877 CG ARG A 104 4.087 8.047 25.918 1.00 12.76 C ATOM 878 CD ARG A 104 4.194 8.213 24.407 1.00 12.98 C ATOM 879 NE ARG A 104 3.190 9.183 23.965 1.00 11.68 N ATOM 880 CZ ARG A 104 1.884 8.907 23.798 1.00 16.02 C ATOM 881 NH1 ARG A 104 1.066 9.887 23.448 1.00 16.52 N ATOM 882 NH2 ARG A 104 1.364 7.674 24.026 1.00 14.91 N ATOM 883 C ARG A 104 4.372 7.836 28.724 1.00 14.93 C ATOM 884 O ARG A 104 5.115 8.780 29.046 1.00 14.63 O ATOM 885 N LEU A 105 3.075 7.793 29.029 1.00 13.25 N ATOM 886 CA LEU A 105 2.340 8.984 29.475 1.00 12.90 C ATOM 887 CB LEU A 105 0.837 8.801 29.283 1.00 13.12 C ATOM 888 CG LEU A 105 0.401 8.723 27.814 1.00 13.13 C ATOM 889 CD1 LEU A 105 −1.124 8.236 27.794 1.00 14.35 C ATOM 890 CD2 LEU A 105 0.669 10.072 27.072 1.00 11.38 C ATOM 891 C LEU A 105 2.661 9.452 30.893 1.00 12.95 C ATOM 892 O LEU A 105 2.952 10.665 31.098 1.00 12.05 O ATOM 893 N ALA A 106 2.626 8.544 31.874 1.00 12.66 N ATOM 894 CA ALA A 106 2.898 8.971 33.269 1.00 13.15 C ATOM 895 CB ALA A 106 2.773 7.778 34.293 1.00 10.91 C ATOM 896 C ALA A 106 4.273 9.643 33.355 1.00 13.75 C ATOM 897 O ALA A 106 4.414 10.774 33.861 1.00 15.38 O ATOM 898 N PRO A 107 5.323 8.962 32.876 1.00 15.07 N ATOM 899 CA PRO A 107 6.636 9.690 32.873 1.00 13.91 C ATOM 900 CB PRO A 107 7.648 8.579 32.608 1.00 14.31 C ATOM 901 CG PRO A 107 6.837 7.480 31.988 1.00 16.27 C ATOM 902 CD PRO A 107 5.458 7.541 32.492 1.00 14.07 C ATOM 903 C PRO A 107 6.867 10.846 31.914 1.00 12.66 C ATOM 904 O PRO A 107 7.740 11.686 32.213 1.00 13.50 O ATOM 905 N LEU A 108 6.192 10.905 30.773 1.00 10.99 N ATOM 906 CA LEU A 108 6.188 12.141 29.991 1.00 12.51 C ATOM 907 CB LEU A 108 5.261 12.056 28.762 1.00 12.84 C ATOM 908 CG LEU A 108 5.153 13.340 27.937 1.00 14.17 C ATOM 909 CD1 LEU A 108 6.553 13.818 27.293 1.00 10.33 C ATOM 910 CD2 LEU A 108 4.084 13.124 26.905 1.00 14.83 C ATOM 911 C LEU A 108 5.711 13.302 30.876 1.00 13.04 C ATOM 912 O LEU A 108 6.333 14.373 30.888 1.00 15.26 O ATOM 913 N TYR A 109 4.604 13.104 31.594 1.00 13.82 N ATOM 914 CA TYR A 109 4.106 14.116 32.509 1.00 13.76 C ATOM 915 CB TYR A 109 2.756 13.735 33.137 1.00 15.29 C ATOM 916 CG TYR A 109 1.689 13.437 32.178 1.00 17.61 C ATOM 917 CD1 TYR A 109 1.481 14.243 31.086 1.00 21.26 C ATOM 918 CE1 TYR A 109 0.472 13.981 30.196 1.00 20.34 C ATOM 919 CZ TYR A 109 −0.325 12.920 30.394 1.00 19.53 C ATOM 920 OH TYR A 109 −1.302 12.681 29.487 1.00 22.88 O ATOM 921 CE2 TYR A 109 −0.169 12.078 31.487 1.00 21.61 C ATOM 922 CD2 TYR A 109 0.852 12.360 32.382 1.00 17.80 C ATOM 923 C TYR A 109 5.073 14.453 33.648 1.00 12.22 C ATOM 924 O TYR A 109 5.205 15.627 33.951 1.00 11.21 O ATOM 925 N ALA A 110 5.701 13.448 34.301 1.00 11.08 N ATOM 926 CA ALA A 110 6.776 13.771 35.262 1.00 11.48 C ATOM 927 CB ALA A 110 7.328 12.511 35.988 1.00 8.23 C ATOM 928 C ALA A 110 7.888 14.600 34.593 1.00 11.82 C ATOM 929 O ALA A 110 8.368 15.531 35.163 1.00 14.31 O ATOM 930 N SER A 111 8.307 14.265 33.378 1.00 12.96 N ATOM 931 CA SER A 111 9.421 14.988 32.747 1.00 13.27 C ATOM 932 CB SER A 111 9.991 14.210 31.527 1.00 10.94 C ATOM 933 OG SER A 111 9.145 14.441 30.410 1.00 16.40 O ATOM 934 C SER A 111 8.994 16.478 32.380 1.00 13.84 C ATOM 935 O SER A 111 9.766 17.421 32.529 1.00 14.85 O ATOM 936 N ALA A 112 7.745 16.670 31.963 1.00 13.58 N ATOM 937 CA ALA A 112 7.219 17.993 31.703 1.00 11.84 C ATOM 938 CB ALA A 112 5.838 17.898 31.051 1.00 10.37 C ATOM 939 C ALA A 112 7.167 18.881 32.974 1.00 11.97 C ATOM 940 O ALA A 112 7.481 20.102 32.900 1.00 10.21 O ATOM 941 N ARG A 113 6.738 18.312 34.105 1.00 12.79 N ATOM 942 CA ARG A 113 6.711 19.070 35.368 1.00 13.87 C ATOM 943 CB ARG A 113 6.120 18.266 36.537 1.00 13.69 C ATOM 944 CG ARG A 113 4.596 18.128 36.421 1.00 15.95 C ATOM 945 CD ARG A 113 3.932 17.387 37.599 1.00 18.47 C ATOM 946 NE ARG A 113 4.346 15.979 37.685 1.00 25.47 N ATOM 947 CZ ARG A 113 3.610 14.918 37.306 1.00 26.94 C ATOM 948 NH1 ARG A 113 2.359 15.082 36.820 1.00 27.58 N ATOM 949 NH2 ARG A 113 4.129 13.691 37.430 1.00 23.12 N ATOM 950 C ARG A 113 8.133 19.554 35.685 1.00 13.41 C ATOM 951 O ARG A 113 8.300 20.667 36.101 1.00 13.78 O ATOM 952 N ALA A 114 9.136 18.699 35.485 1.00 12.35 N ATOM 953 CA ALA A 114 10.477 19.029 35.873 1.00 11.15 C ATOM 954 CB ALA A 114 11.362 17.762 35.926 1.00 10.92 C ATOM 955 C ALA A 114 11.048 20.101 34.903 1.00 11.85 C ATOM 956 O ALA A 114 11.667 21.066 35.366 1.00 9.24 O ATOM 957 N LEU A 115 10.772 19.976 33.598 1.00 10.88 N ATOM 958 CA LEU A 115 11.277 20.980 32.619 1.00 13.38 C ATOM 959 CB LEU A 115 11.005 20.488 31.163 1.00 12.74 C ATOM 960 CG LEU A 115 11.715 21.035 29.972 1.00 13.69 C ATOM 961 CD1 LEU A 115 13.238 21.172 30.317 1.00 16.09 C ATOM 962 CD2 LEU A 115 11.542 20.106 28.770 1.00 14.91 C ATOM 963 C LEU A 115 10.541 22.315 32.866 1.00 13.80 C ATOM 964 O LEU A 115 11.171 23.365 32.900 1.00 16.02 O ATOM 965 N TRP A 116 9.221 22.271 33.054 1.00 13.64 N ATOM 966 CA TRP A 116 8.506 23.480 33.356 1.00 13.88 C ATOM 967 CB TRP A 116 7.016 23.231 33.466 1.00 13.31 C ATOM 968 CG TRP A 116 6.262 23.224 32.097 1.00 16.85 C ATOM 969 CD1 TRP A 116 5.436 22.187 31.593 1.00 13.15 C ATOM 970 NE1 TRP A 116 4.893 22.561 30.385 1.00 14.92 N ATOM 971 CE2 TRP A 116 5.315 23.822 30.064 1.00 14.46 C ATOM 972 CD2 TRP A 116 6.161 24.293 31.133 1.00 15.63 C ATOM 973 CE3 TRP A 116 6.702 25.593 31.054 1.00 16.77 C ATOM 974 CZ3 TRP A 116 6.375 26.372 29.943 1.00 16.02 C ATOM 975 CH2 TRP A 116 5.537 25.863 28.890 1.00 14.85 C ATOM 976 CZ2 TRP A 116 5.012 24.596 28.944 1.00 15.66 C ATOM 977 C TRP A 116 9.001 24.198 34.620 1.00 13.49 C ATOM 978 O TRP A 116 9.011 25.426 34.672 1.00 12.26 O ATOM 979 N LEU A 117 9.353 23.448 35.655 1.00 14.45 N ATOM 980 CA LEU A 117 9.980 24.047 36.825 1.00 15.88 C ATOM 981 CB LEU A 117 10.101 23.020 37.961 1.00 15.64 C ATOM 982 CG LEU A 117 10.651 23.436 39.298 1.00 20.17 C ATOM 983 CD1 LEU A 117 9.846 24.607 39.951 1.00 21.46 C ATOM 984 CD2 LEU A 117 10.601 22.165 40.221 1.00 18.31 C ATOM 985 C LEU A 117 11.317 24.684 36.465 1.00 15.24 C ATOM 986 O LEU A 117 11.608 25.778 36.937 1.00 16.29 O ATOM 987 N LEU A 118 12.133 24.047 35.643 1.00 14.71 N ATOM 988 CA LEU A 118 13.381 24.693 35.193 1.00 15.37 C ATOM 989 CB LEU A 118 14.264 23.778 34.337 1.00 14.41 C ATOM 990 CG LEU A 118 15.072 22.673 35.008 1.00 15.73 C ATOM 991 CD1 LEU A 118 15.681 21.656 33.970 1.00 13.78 C ATOM 992 CD2 LEU A 118 16.144 23.343 35.876 1.00 10.27 C ATOM 993 C LEU A 118 13.079 25.990 34.420 1.00 14.94 C ATOM 994 O LEU A 118 13.794 26.958 34.586 1.00 15.78 O ATOM 995 N VAL A 119 12.047 25.991 33.566 1.00 14.65 N ATOM 996 CA VAL A 119 11.725 27.163 32.816 1.00 11.84 C ATOM 997 CB VAL A 119 10.594 26.871 31.799 1.00 11.96 C ATOM 998 CG1 VAL A 119 9.910 28.176 31.352 1.00 10.15 C ATOM 999 CG2 VAL A 119 11.076 26.026 30.581 1.00 8.10 C ATOM 1000 C VAL A 119 11.326 28.296 33.813 1.00 13.56 C ATOM 1001 O VAL A 119 11.699 29.443 33.624 1.00 14.32 O ATOM 1002 N ALA A 120 10.551 27.964 34.851 1.00 13.23 N ATOM 1003 CA ALA A 120 10.071 28.922 35.801 1.00 13.63 C ATOM 1004 CB ALA A 120 9.006 28.329 36.725 1.00 13.60 C ATOM 1005 C ALA A 120 11.226 29.453 36.597 1.00 13.56 C ATOM 1006 O ALA A 120 11.254 30.632 36.874 1.00 13.30 O ATOM 1007 N LEU A 121 12.174 28.602 36.977 1.00 13.08 N ATOM 1008 CA LEU A 121 13.325 29.118 37.697 1.00 14.20 C ATOM 1009 CB LEU A 121 14.181 28.004 38.352 1.00 13.22 C ATOM 1010 CG LEU A 121 13.491 27.071 39.344 1.00 13.38 C ATOM 1011 CD1 LEU A 121 14.549 26.035 39.797 1.00 11.02 C ATOM 1012 CD2 LEU A 121 12.805 27.806 40.508 1.00 13.39 C ATOM 1013 C LEU A 121 14.221 29.994 36.809 1.00 13.20 C ATOM 1014 O LEU A 121 14.803 30.929 37.305 1.00 14.45 O ATOM 1015 N ALA A 122 14.340 29.662 35.520 1.00 14.22 N ATOM 1016 CA ALA A 122 15.103 30.471 34.574 1.00 14.30 C ATOM 1017 CB ALA A 122 15.233 29.771 33.270 1.00 12.02 C ATOM 1018 C ALA A 122 14.452 31.876 34.419 1.00 14.09 C ATOM 1019 O ALA A 122 15.144 32.866 34.502 1.00 15.03 O ATOM 1020 N ALA A 123 13.127 31.932 34.286 1.00 15.23 N ATOM 1021 CA ALA A 123 12.365 33.196 34.181 1.00 14.48 C ATOM 1022 CB ALA A 123 10.905 32.912 33.818 1.00 13.53 C ATOM 1023 C ALA A 123 12.478 34.103 35.445 1.00 15.58 C ATOM 1024 O ALA A 123 12.692 35.291 35.312 1.00 15.67 O ATOM 1025 N LEU A 124 12.328 33.521 36.639 1.00 14.48 N ATOM 1026 CA LEU A 124 12.529 34.188 37.883 1.00 16.04 C ATOM 1027 CB LEU A 124 12.177 33.310 39.120 1.00 15.29 C ATOM 1028 CG LEU A 124 10.724 32.882 39.232 1.00 17.42 C ATOM 1029 CD1 LEU A 124 10.507 31.731 40.252 1.00 15.84 C ATOM 1030 CD2 LEU A 124 9.740 34.103 39.462 1.00 17.06 C ATOM 1031 C LEU A 124 13.940 34.692 38.002 1.00 15.91 C ATOM 1032 O LEU A 124 14.103 35.816 38.407 1.00 17.85 O ATOM 1033 N GLY A 125 14.959 33.925 37.633 1.00 15.26 N ATOM 1034 CA GLY A 125 16.266 34.465 37.742 1.00 14.67 C ATOM 1035 C GLY A 125 16.490 35.642 36.785 1.00 15.34 C ATOM 1036 O GLY A 125 17.205 36.605 37.148 1.00 13.70 O ATOM 1037 N LEU A 126 16.005 35.516 35.535 1.00 15.03 N ATOM 1038 CA LEU A 126 16.145 36.573 34.547 1.00 14.38 C ATOM 1039 CB LEU A 126 15.715 36.133 33.141 1.00 12.20 C ATOM 1040 CG LEU A 126 16.729 35.176 32.490 1.00 12.52 C ATOM 1041 CD1 LEU A 126 16.040 34.599 31.253 1.00 9.80 C ATOM 1042 CD2 LEU A 126 18.055 35.833 32.135 1.00 2.00 C ATOM 1043 C LEU A 126 15.308 37.807 35.002 1.00 15.97 C ATOM 1044 O LEU A 126 15.780 38.957 34.864 1.00 16.88 O ATOM 1045 N LEU A 127 14.107 37.604 35.537 1.00 14.84 N ATOM 1046 CA LEU A 127 13.376 38.715 36.090 1.00 17.03 C ATOM 1047 CB LEU A 127 12.068 38.264 36.654 1.00 17.65 C ATOM 1048 CG LEU A 127 10.992 38.413 35.627 1.00 26.91 C ATOM 1049 CD1 LEU A 127 9.886 37.317 35.933 1.00 32.60 C ATOM 1050 CD2 LEU A 127 10.454 39.885 35.581 1.00 29.73 C ATOM 1051 C LEU A 127 14.177 39.431 37.221 1.00 16.39 C ATOM 1052 O LEU A 127 14.205 40.641 37.238 1.00 16.26 O ATOM 1053 N ALA A 128 14.745 38.683 38.181 1.00 16.11 N ATOM 1054 CA ALA A 128 15.560 39.301 39.247 1.00 15.78 C ATOM 1055 CB ALA A 128 16.001 38.292 40.264 1.00 15.58 C ATOM 1056 C ALA A 128 16.761 40.032 38.638 1.00 15.63 C ATOM 1057 O ALA A 128 17.159 41.070 39.122 1.00 17.53 O ATOM 1058 N HIS A 129 17.294 39.556 37.535 1.00 16.41 N ATOM 1059 CA HIS A 129 18.379 40.271 36.890 1.00 16.54 C ATOM 1060 CB HIS A 129 19.118 39.371 35.890 1.00 17.13 C ATOM 1061 CG HIS A 129 20.251 40.065 35.217 1.00 17.82 C ATOM 1062 ND1 HIS A 129 21.496 40.185 35.797 1.00 17.71 N ATOM 1063 CE1 HIS A 129 22.282 40.910 35.018 1.00 17.15 C ATOM 1064 NE2 HIS A 129 21.590 41.268 33.950 1.00 17.75 N ATOM 1065 CD2 HIS A 129 20.323 40.731 34.035 1.00 17.93 C ATOM 1066 C HIS A 129 17.954 41.614 36.223 1.00 17.26 C ATOM 1067 O HIS A 129 18.664 42.605 36.407 1.00 17.60 O ATOM 1068 N PHE A 130 16.823 41.646 35.480 1.00 15.37 N ATOM 1069 CA PHE A 130 16.438 42.789 34.671 1.00 15.70 C ATOM 1070 CB PHE A 130 15.861 42.365 33.292 1.00 14.48 C ATOM 1071 CG PHE A 130 16.875 41.811 32.333 1.00 14.26 C ATOM 1072 CD1 PHE A 130 17.803 42.661 31.695 1.00 12.46 C ATOM 1073 CE1 PHE A 130 18.726 42.117 30.736 1.00 14.66 C ATOM 1074 CZ PHE A 130 18.683 40.747 30.426 1.00 11.28 C ATOM 1075 CE2 PHE A 130 17.741 39.898 31.074 1.00 9.83 C ATOM 1076 CD2 PHE A 130 16.863 40.436 32.007 1.00 9.24 C ATOM 1077 C PHE A 130 15.468 43.808 35.339 1.00 16.84 C ATOM 1078 O PHE A 130 15.513 44.975 34.988 1.00 15.03 O ATOM 1079 N LEU A 131 14.599 43.368 36.263 1.00 18.31 N ATOM 1080 CA LEU A 131 13.485 44.202 36.725 1.00 19.33 C ATOM 1081 CB LEU A 131 12.471 43.345 37.475 1.00 21.55 C ATOM 1082 CG LEU A 131 11.072 43.868 37.754 1.00 24.78 C ATOM 1083 CD1 LEU A 131 10.360 44.192 36.448 1.00 24.49 C ATOM 1084 CD2 LEU A 131 10.345 42.759 38.512 1.00 27.31 C ATOM 1085 C LEU A 131 13.941 45.434 37.535 1.00 19.75 C ATOM 1086 O LEU A 131 13.441 46.532 37.272 1.00 17.96 O ATOM 1087 N PRO A 132 14.886 45.269 38.500 1.00 19.97 N ATOM 1088 CA PRO A 132 15.345 46.415 39.333 1.00 20.32 C ATOM 1089 CB PRO A 132 16.443 45.791 40.248 1.00 20.94 C ATOM 1090 CG PRO A 132 15.921 44.302 40.402 1.00 19.47 C ATOM 1091 CD PRO A 132 15.533 44.012 38.944 1.00 21.77 C ATOM 1092 C PRO A 132 15.823 47.580 38.503 1.00 19.76 C ATOM 1093 O PRO A 132 15.265 48.671 38.616 1.00 20.31 O ATOM 1094 N ALA A 133 16.756 47.318 37.595 1.00 18.26 N ATOM 1095 CA ALA A 133 17.251 48.361 36.768 1.00 16.31 C ATOM 1096 CB ALA A 133 18.521 47.924 36.014 1.00 14.32 C ATOM 1097 C ALA A 133 16.206 48.935 35.832 1.00 14.97 C ATOM 1098 O ALA A 133 16.216 50.119 35.606 1.00 16.49 O ATOM 1099 N ALA A 134 15.304 48.136 35.273 1.00 14.39 N ATOM 1100 CA ALA A 134 14.215 48.705 34.473 1.00 13.98 C ATOM 1101 CB ALA A 134 13.452 47.588 33.660 1.00 13.38 C ATOM 1102 C ALA A 134 13.250 49.577 35.280 1.00 14.32 C ATOM 1103 O ALA A 134 12.835 50.671 34.786 1.00 14.38 O ATOM 1104 N LEU A 135 12.894 49.147 36.508 1.00 14.05 N ATOM 1105 CA LEU A 135 11.992 49.957 37.317 1.00 15.12 C ATOM 1106 CB LEU A 135 11.510 49.203 38.549 1.00 16.20 C ATOM 1107 CG LEU A 135 10.601 47.982 38.289 1.00 18.97 C ATOM 1108 CD1 LEU A 135 10.218 47.302 39.601 1.00 19.42 C ATOM 1109 CD2 LEU A 135 9.329 48.362 37.460 1.00 19.36 C ATOM 1110 C LEU A 135 12.655 51.301 37.733 1.00 15.26 C ATOM 1111 O LEU A 135 12.018 52.382 37.734 1.00 15.72 O ATOM 1112 N ARG A 136 13.938 51.210 38.077 1.00 14.02 N ATOM 1113 CA ARG A 136 14.716 52.358 38.455 1.00 13.62 C ATOM 1114 CB ARG A 136 16.122 51.952 38.796 1.00 11.70 C ATOM 1115 CG ARG A 136 16.799 53.193 39.199 1.00 17.23 C ATOM 1116 CD ARG A 136 17.999 53.021 39.977 1.00 21.91 C ATOM 1117 NE ARG A 136 19.048 52.500 39.145 1.00 27.85 N ATOM 1118 CZ ARG A 136 20.322 52.512 39.502 1.00 32.97 C ATOM 1119 NH1 ARG A 136 20.721 53.038 40.656 1.00 29.38 N ATOM 1120 NH2 ARG A 136 21.211 51.993 38.692 1.00 38.10 N ATOM 1121 C ARG A 136 14.766 53.387 37.340 1.00 12.04 C ATOM 1122 O ARG A 136 14.522 54.551 37.573 1.00 13.00 O ATOM 1123 N ALA A 137 15.048 52.934 36.118 1.00 13.52 N ATOM 1124 CA ALA A 137 15.091 53.810 34.952 1.00 13.62 C ATOM 1125 CB ALA A 137 15.637 53.013 33.709 1.00 12.85 C ATOM 1126 C ALA A 137 13.718 54.411 34.661 1.00 13.19 C ATOM 1127 O ALA A 137 13.621 55.597 34.361 1.00 13.65 O ATOM 1128 N ALA A 138 12.660 53.598 34.724 1.00 13.79 N ATOM 1129 CA ALA A 138 11.287 54.111 34.538 1.00 13.40 C ATOM 1130 CB ALA A 138 10.256 52.966 34.705 1.00 12.19 C ATOM 1131 C ALA A 138 11.048 55.265 35.564 1.00 14.42 C ATOM 1132 O ALA A 138 10.663 56.419 35.209 1.00 14.09 O ATOM 1133 N LEU A 139 11.329 54.972 36.833 1.00 15.58 N ATOM 1134 CA LEU A 139 11.163 55.955 37.911 1.00 16.41 C ATOM 1135 CB LEU A 139 11.494 55.301 39.237 1.00 17.46 C ATOM 1136 CG LEU A 139 10.332 54.701 40.025 1.00 20.93 C ATOM 1137 CD1 LEU A 139 10.774 53.393 40.715 1.00 19.31 C ATOM 1138 CD2 LEU A 139 9.858 55.847 41.000 1.00 24.20 C ATOM 1139 C LEU A 139 12.007 57.215 37.782 1.00 16.65 C ATOM 1140 O LEU A 139 11.516 58.304 38.011 1.00 16.20 O ATOM 1141 N LEU A 140 13.298 57.083 37.466 1.00 17.70 N ATOM 1142 CA LEU A 140 14.119 58.296 37.257 1.00 17.48 C ATOM 1143 CB LEU A 140 15.571 57.980 36.905 1.00 17.06 C ATOM 1144 CG LEU A 140 16.413 57.309 38.015 1.00 18.21 C ATOM 1145 CD1 LEU A 140 17.753 56.754 37.439 1.00 18.45 C ATOM 1146 CD2 LEU A 140 16.610 58.209 39.236 1.00 15.29 C ATOM 1147 C LEU A 140 13.532 59.196 36.165 1.00 18.39 C ATOM 1148 O LEU A 140 13.619 60.408 36.287 1.00 18.39 O ATOM 1149 N GLY A 141 12.962 58.573 35.123 1.00 19.17 N ATOM 1150 CA GLY A 141 12.262 59.211 34.040 1.00 20.51 C ATOM 1151 C GLY A 141 11.116 60.082 34.528 1.00 21.91 C ATOM 1152 O GLY A 141 10.976 61.202 34.066 1.00 22.14 O ATOM 1153 N ARG A 142 10.313 59.579 35.468 1.00 23.33 N ATOM 1154 CA ARG A 142 9.240 60.350 36.091 1.00 25.41 C ATOM 1155 CB ARG A 142 8.284 59.477 36.901 1.00 24.99 C ATOM 1156 CG ARG A 142 7.928 58.177 36.272 1.00 30.09 C ATOM 1157 CD ARG A 142 6.477 58.109 35.945 1.00 38.07 C ATOM 1158 NE ARG A 142 6.024 59.304 35.245 1.00 44.22 N ATOM 1159 CZ ARG A 142 6.452 59.669 34.041 1.00 47.61 C ATOM 1160 NH1 ARG A 142 5.970 60.777 33.474 1.00 48.87 N ATOM 1161 NH2 ARG A 142 7.364 58.928 33.411 1.00 47.82 N ATOM 1162 C ARG A 142 9.754 61.399 37.049 1.00 26.59 C ATOM 1163 O ARG A 142 9.043 62.348 37.292 1.00 26.95 O ATOM 1164 N LEU A 143 10.960 61.245 37.602 1.00 27.81 N ATOM 1165 CA ALEU A 143 11.450 62.097 38.712 0.50 28.31 C ATOM 1166 CA BLEU A 143 11.319 62.085 38.717 0.50 28.43 C ATOM 1167 CB ALEU A 143 12.899 61.769 39.167 0.50 28.08 C ATOM 1168 CB BLEU A 143 12.548 61.549 39.462 0.50 27.84 C ATOM 1169 CG ALEU A 143 13.450 62.537 40.406 0.50 27.82 C ATOM 1170 CG BLEU A 143 12.219 60.664 40.682 0.50 26.49 C ATOM 1171 CD1 ALEU A 143 13.158 61.781 41.696 0.50 27.48 C ATOM 1172 CD1 BLEU A 143 12.798 61.289 41.938 0.50 26.64 C ATOM 1173 CD2 ALEU A 143 14.929 62.898 40.358 0.50 26.74 C ATOM 1174 CD2 BLEU A 143 10.719 60.404 40.870 0.50 24.63 C ATOM 1175 C LEU A 143 11.353 63.574 38.394 1.00 29.56 C ATOM 1176 O LEU A 143 11.038 64.372 39.274 1.00 29.09 O ATOM 1177 N ARG A 144 11.652 63.945 37.143 1.00 32.10 N ATOM 1178 CA ARG A 144 11.623 65.397 36.701 1.00 35.18 C ATOM 1179 CB ARG A 144 11.710 65.523 35.170 1.00 35.69 C ATOM 1180 CG ARG A 144 10.819 64.496 34.440 1.00 36.66 C ATOM 1181 CD ARG A 144 9.426 65.058 34.107 1.00 38.59 C ATOM 1182 NE ARG A 144 8.348 64.080 34.345 1.00 38.54 N ATOM 1183 CZ ARG A 144 7.336 64.243 35.208 1.00 38.75 C ATOM 1184 NH1 ARG A 144 7.220 65.351 35.923 1.00 38.78 N ATOM 1185 NH2 ARG A 144 6.417 63.300 35.361 1.00 39.05 N ATOM 1186 C ARG A 144 10.392 66.179 37.226 1.00 36.66 C ATOM 1187 O ARG A 144 9.369 66.281 36.541 1.00 37.30 O ATOM 1188 N THR A 145 10.553 66.781 38.414 1.00 37.68 N ATOM 1189 CA THR A 145 9.473 67.132 39.352 1.00 37.91 C ATOM 1190 CB THR A 145 9.161 68.652 39.248 1.00 38.56 C ATOM 1191 OG1 THR A 145 10.419 69.339 39.132 1.00 40.06 O ATOM 1192 CG2 THR A 145 8.349 69.231 40.487 1.00 39.02 C ATOM 1193 C THR A 145 8.280 66.121 39.314 1.00 37.66 C ATOM 1194 O THR A 145 8.162 65.179 40.106 1.00 36.34 O ATOM 1195 OXT THR A 145 7.397 66.142 38.473 1.00 37.90 O ATOM 1196 NI NI B 1 49.619 35.321 35.324 0.33 43.64 NI ATOM 1197 NI NI B 2 36.032 36.034 36.032 0.33 34.18 NI ATOM 1198 O6′ LMT C 2 −2.641 14.467 21.544 1.00 55.59 O ATOM 1199 C6′ LMT C 2 −3.020 13.503 22.520 1.00 65.46 C ATOM 1200 C5′ LMT C 2 −1.903 12.590 23.122 1.00 68.25 C ATOM 1201 C4′ LMT C 2 −2.524 11.311 23.768 1.00 71.67 C ATOM 1202 C3′ LMT C 2 −2.897 11.304 25.278 1.00 69.12 C ATOM 1203 O3′ LMT C 2 −4.153 10.597 25.541 1.00 65.82 O ATOM 1204 C2′ LMT C 2 −2.816 12.699 25.942 1.00 68.48 C ATOM 1205 O2′ LMT C 2 −2.892 12.577 27.385 1.00 69.28 O ATOM 1206 O1* LMT C 2 −1.587 10.255 23.638 1.00 80.39 O ATOM 1207 C1* LMT C 2 −2.340 9.073 23.413 1.00 88.39 C ATOM 1208 O5* LMT C 2 −2.310 8.780 22.004 1.00 92.28 O ATOM 1209 C5* LMT C 2 −3.102 7.587 21.990 1.00 94.73 C ATOM 1210 C6* LMT C 2 −4.226 7.614 20.917 1.00 96.13 C ATOM 1211 O6* LMT C 2 −4.478 8.959 20.439 1.00 99.22 O ATOM 1212 C4* LMT C 2 −2.140 6.376 22.259 1.00 92.70 C ATOM 1213 O4* LMT C 2 −1.123 6.201 21.236 1.00 89.99 O ATOM 1214 C3* LMT C 2 −1.518 6.588 23.678 1.00 90.17 C ATOM 1215 O3* LMT C 2 −1.787 5.546 24.633 1.00 87.74 O ATOM 1216 C2* LMT C 2 −1.994 7.879 24.373 1.00 90.31 C ATOM 1217 O2* LMT C 2 −3.100 7.571 25.287 1.00 90.99 O ATOM 1218 O5′ LMT C 2 −1.035 13.203 24.103 1.00 64.23 O ATOM 1219 C1′ LMT C 2 −1.643 13.598 25.394 1.00 66.28 C ATOM 1220 O1′ LMT C 2 −0.652 13.915 26.382 1.00 61.22 O ATOM 1221 C1 LMT C 2 −0.324 15.293 26.271 1.00 59.74 C ATOM 1222 C2 LMT C 2 0.129 15.941 27.582 1.00 58.38 C ATOM 1223 C3 LMT C 2 1.652 16.029 27.567 1.00 53.65 C ATOM 1224 C4 LMT C 2 2.152 17.260 28.279 1.00 47.24 C ATOM 1225 C5 LMT C 2 3.653 17.040 28.379 1.00 45.00 C ATOM 1226 C6 LMT C 2 4.473 17.301 27.120 1.00 40.50 C ATOM 1227 C7 LMT C 2 4.391 18.766 26.805 1.00 38.80 C ATOM 1228 C8 LMT C 2 5.784 19.270 26.461 1.00 39.22 C ATOM 1229 C9 LMT C 2 5.984 20.624 27.142 1.00 41.72 C ATOM 1230 C10 LMT C 2 7.383 21.257 27.072 1.00 40.00 C ATOM 1231 C11 LMT C 2 7.796 21.777 28.445 1.00 42.73 C ATOM 1232 C12 LMT C 2 8.884 22.860 28.345 1.00 45.65 C ATOM 1233 O31 GTT D 1 7.260 11.767 19.720 1.00 18.18 O ATOM 1234 C3 GTT D 1 6.534 10.745 19.928 1.00 23.39 C ATOM 1235 O32 GTT D 1 6.794 9.681 19.307 1.00 22.21 O ATOM 1236 CA3 GTT D 1 5.385 10.720 20.937 1.00 21.49 C ATOM 1237 N3 GTT D 1 5.108 12.040 21.461 1.00 17.33 N ATOM 1238 C2 GTT D 1 4.906 12.262 22.759 1.00 18.28 C ATOM 1239 O2 GTT D 1 5.170 11.234 23.600 1.00 19.19 O ATOM 1240 CA2 GTT D 1 4.330 13.562 23.268 1.00 16.91 C ATOM 1241 CB2 GTT D 1 2.906 13.185 23.759 1.00 19.79 C ATOM 1242 SG2 GTT D 1 1.808 12.751 22.382 1.00 19.29 S ATOM 1243 N2 GTT D 1 4.231 14.575 22.163 1.00 21.49 N ATOM 1244 CD1 GTT D 1 5.157 15.515 21.860 1.00 15.20 C ATOM 1245 OE1 GTT D 1 6.314 15.422 22.562 1.00 19.82 O ATOM 1246 CG1 GTT D 1 4.983 16.500 20.708 1.00 14.16 C ATOM 1247 CB1 GTT D 1 6.308 16.329 20.014 1.00 15.79 C ATOM 1248 CA1 GTT O 1 6.307 15.434 18.773 1.00 23.56 C ATOM 1249 N1 GTT D 1 7.583 15.142 18.203 1.00 17.29 N ATOM 1250 C1 GTT D 1 5.393 14.226 18.497 1.00 22.82 C ATOM 1251 O11 GTT D 1 4.484 13.795 19.226 1.00 21.17 O ATOM 1252 O12 GTT D 1 5.580 13.736 17.383 1.00 19.19 O ATOM 1253 O2 PLM E 1 26.974 33.632 38.899 1.00 66.56 O ATOM 1254 C1 PLM E 1 27.406 32.626 38.230 1.00 66.81 C ATOM 1255 O1 PLM E 1 27.017 31.447 38.519 1.00 64.62 O ATOM 1256 C2 PLM E 1 28.419 32.836 37.100 1.00 64.42 C ATOM 1257 C3 PLM E 1 28.693 31.511 36.394 1.00 60.12 C ATOM 1258 C4 PLM E 1 29.921 31.548 35.493 1.00 59.14 C ATOM 1259 C5 PLM E 1 29.759 32.417 34.250 1.00 56.91 C ATOM 1260 C6 PLM E 1 29.137 31.618 33.124 1.00 54.09 C ATOM 1261 C7 PLM E 1 28.634 32.575 32.060 1.00 51.22 C ATOM 1262 C8 PLM E 1 28.276 31.808 30.785 1.00 47.04 C ATOM 1263 C9 PLM E 1 27.522 30.474 30.940 1.00 46.76 C ATOM 1264 C10 PLM E 1 27.144 29.952 29.535 1.00 44.05 C ATOM 1265 C11 PLM E 1 26.288 28.712 29.447 1.00 41.17 C ATOM 1266 C12 PLM E 1 25.119 29.008 28.521 1.00 37.05 C ATOM 1267 C13 PLM E 1 24.761 27.741 27.783 1.00 33.21 C ATOM 1268 C14 PLM E 1 23.369 27.762 27.137 1.00 35.38 C ATOM 1269 C15 PLM E 1 23.143 26.418 26.449 1.00 35.82 C ATOM 1270 C16 PLM E 1 22.860 26.760 25.007 1.00 36.18 C ATOM 1272 C1 PLM E 2 11.914 38.040 26.633 1.00 48.53 C ATOM 1274 C2 PLM E 2 13.174 37.970 25.790 1.00 44.77 C ATOM 1275 C3 PLM E 2 13.602 39.369 25.287 1.00 44.35 C ATOM 1276 C4 PLM E 2 15.114 39.474 24.969 1.00 38.32 C ATOM 1277 C5 PLM E 2 15.515 40.918 24.728 1.00 37.07 C ATOM 1278 C6 PLM E 2 16.706 41.173 23.807 1.00 35.48 C ATOM 1279 C7 PLM E 2 16.774 42.671 23.526 1.00 37.05 C ATOM 1280 C8 PLM E 2 17.978 43.129 22.653 1.00 37.63 C ATOM 1281 C9 PLM E 2 18.500 44.556 22.928 1.00 39.61 C ATOM 1282 C10 PLM E 2 19.561 45.130 21.927 1.00 36.56 C ATOM 1290 C1 PLM E 3 11.541 46.276 43.832 1.00 39.81 C ATOM 1292 C2 PLM E 3 12.716 46.969 43.161 1.00 39.10 C ATOM 1293 C3 PLM E 3 12.315 48.228 42.438 1.00 35.98 C ATOM 1294 C4 PLM E 3 13.068 49.485 42.861 1.00 40.15 C ATOM 1295 C5 PLM E 3 14.269 49.934 42.035 1.00 36.54 C ATOM 1296 C6 PLM E 3 15.487 49.927 42.964 1.00 37.54 C ATOM 1297 C7 PLM E 3 16.859 50.306 42.421 1.00 36.68 C ATOM 1298 C8 PLM E 3 17.845 49.142 42.450 1.00 41.16 C ATOM 1299 C9 PLM E 3 19.322 49.524 42.505 1.00 44.23 C ATOM 1300 C10 PLM E 3 20.060 48.981 41.279 1.00 47.26 C ATOM 1308 C1 PLM E 4 11.814 37.183 31.848 1.00 45.82 C ATOM 1310 C2 PLM E 4 12.943 37.762 30.970 1.00 45.75 C ATOM 1311 C3 PLM E 4 12.893 39.300 30.870 1.00 42.36 C ATOM 1312 C4 PLM E 4 13.992 39.810 29.928 1.00 39.54 C ATOM 1313 C5 PLM E 4 13.894 41.291 29.589 1.00 37.76 C ATOM 1314 C6 PLM E 4 15.128 41.823 28.881 1.00 36.66 C ATOM 1315 C7 PLM E 4 15.019 43.285 28.388 1.00 37.90 C ATOM 1316 C8 PLM E 4 16.317 44.077 28.668 1.00 39.17 C ATOM 1317 C9 PLM E 4 16.632 45.429 27.993 1.00 41.51 C ATOM 1318 C10 PLM E 4 17.991 46.027 28.467 1.00 39.52 C ATOM 1326 C1 PLM E 5 11.321 43.101 32.669 1.00 48.99 C ATOM 1328 C2 PLM E 5 12.190 44.150 32.016 1.00 48.28 C ATOM 1329 C3 PLM E 5 11.457 44.966 30.951 1.00 50.96 C ATOM 1330 C4 PLM E 5 12.490 45.898 30.276 1.00 54.37 C ATOM 1331 C5 PLM E 5 11.911 47.042 29.423 1.00 55.82 C ATOM 1344 C1 PLM E 6 18.081 −0.222 32.874 1.00 49.57 C ATOM 1346 C2 PLM E 6 19.428 0.454 33.122 1.00 49.65 C ATOM 1347 C3 PLM E 6 19.538 1.691 32.234 1.00 44.94 C ATOM 1348 C4 PLM E 6 20.973 2.059 31.885 1.00 41.84 C ATOM 1349 C5 PLM E 6 20.991 3.576 31.764 1.00 38.05 C ATOM 1350 C6 PLM E 6 22.353 4.225 31.633 1.00 41.48 C ATOM 1351 C7 PLM E 6 22.231 5.718 31.962 1.00 42.77 C ATOM 1352 C8 PLM E 6 23.564 6.373 32.261 1.00 42.18 C ATOM 1361 S SO4 F 1 −0.212 0.680 23.119 0.50 38.20 S ATOM 1362 O1 SO4 F 1 −0.012 −0.447 24.080 0.50 37.58 O ATOM 1363 O2 SO4 F 1 1.038 0.841 22.328 0.50 32.09 O ATOM 1364 O3 SO4 F 1 −1.316 0.327 22.206 0.50 35.26 O ATOM 1365 O4 SO4 F 1 −0.573 1.819 23.985 0.50 30.18 O ATOM 1366 O HOH G 1 −0.943 7.401 32.542 1.00 37.80 O ATOM 1367 O HOH G 2 23.768 −2.017 23.464 1.00 50.16 O ATOM 1368 O HOH G 3 24.405 25.638 44.557 1.00 30.72 O ATOM 1369 O HOH G 4 8.539 15.180 38.179 1.00 35.64 O ATOM 1370 O HOH G 5 12.649 −4.140 6.571 1.00 32.67 O ATOM 1371 O HOH G 6 49.199 31.327 29.456 1.00 42.68 O ATOM 1372 O HOH G 7 19.364 −3.454 3.849 1.00 35.88 O ATOM 1373 O HOH G 8 22.454 22.448 22.453 0.33 27.52 O ATOM 1374 O HOH G 9 24.180 28.825 42.845 1.00 31.64 O ATOM 1375 O HOH G 10 15.726 20.889 19.798 1.00 28.20 O ATOM 1376 O HOH G 11 4.869 3.908 32.695 1.00 23.56 O ATOM 1377 O HOH G 12 12.549 20.952 20.270 1.00 26.41 O ATOM 1378 O HOH G 13 −0.641 2.101 32.565 1.00 30.52 O ATOM 1379 O HOH G 14 1.356 4.200 33.433 1.00 41.58 O ATOM 1380 O HOH G 15 23.516 −1.627 20.788 1.00 27.46 O ATOM 1381 O HOH G 16 12.705 51.071 31.777 1.00 39.06 O ATOM 1382 O HOH G 17 19.696 45.528 32.849 1.00 46.56 O ATOM 1383 O HOH G 18 20.332 −4.259 11.486 1.00 56.74 O ATOM 1384 O HOH G 19 6.083 −4.312 9.581 1.00 52.29 O ATOM 1385 O HOH G 20 10.605 −5.685 10.001 1.00 45.47 O ATOM 1386 O HOH G 21 9.714 16.613 28.435 1.00 30.94 O ATOM 1387 O HOH G 22 29.550 23.798 41.176 1.00 24.02 O ATOM 1388 O HOH G 23 19.770 −7.178 19.171 1.00 43.78 O ATOM 1389 O HOH G 24 −0.298 0.404 28.375 0.50 17.68 O ATOM 1390 O HOH G 25 19.502 36.373 38.692 1.00 28.51 O ATOM 1391 O HOH G 26 18.464 10.008 38.963 1.00 47.22 O ATOM 1392 O HOH G 27 17.027 13.019 27.868 1.00 23.53 O ATOM 1393 O HOH G 28 16.918 −11.145 14.469 1.00 45.82 O ATOM 1394 O HOH G 29 3.177 11.600 36.108 1.00 30.70 O ATOM 1395 O HOH G 30 16.303 −2.200 22.254 1.00 35.62 O ATOM 1396 O HOH G 31 3.550 1.641 14.248 1.00 38.31 O ATOM 1397 O HOH G 32 8.799 3.171 32.766 1.00 31.96 O ATOM 1398 O HOH G 33 6.518 5.654 13.528 1.00 25.16 O ATOM 1399 O HOH G 34 −0.568 −2.259 15.350 1.00 38.76 O ATOM 1400 O HOH G 35 11.300 −1.161 28.084 1.00 30.49 O ATOM 1401 O HOH G 36 18.621 45.148 37.681 1.00 34.44 O ATOM 1402 O HOH G 37 8.931 6.171 12.377 1.00 37.11 O ATOM 1403 O HOH G 38 19.279 −0.636 3.034 1.00 40.60 O ATOM 1404 O HOH G 39 7.065 7.091 7.076 0.33 38.56 O ATOM 1405 O HOH G 40 5.120 1.278 9.497 1.00 47.24 O ATOM 1406 O HOH G 41 3.122 −2.767 34.303 1.00 55.08 O ATOM 1407 O HOH G 42 16.405 0.431 35.012 1.00 60.69 O ATOM 1408 O HOH G 43 9.341 56.829 32.953 1.00 47.19 O ATOM 1409 O HOH G 44 13.749 2.875 35.782 1.00 46.75 O ATOM 1410 O HOH G 45 21.044 −4.632 24.353 1.00 48.95 O ATOM 1411 O HOH G 46 17.960 17.972 18.023 0.33 21.66 O ATOM 1412 O HOH G 47 23.465 −4.351 19.223 1.00 46.63 O ATOM 1413 O HOH G 48 22.105 −6.228 19.910 1.00 40.95 O ATOM 1414 O HOH G 49 13.571 −13.572 13.572 0.33 39.27 O ATOM 1415 O HOH G 50 7.079 52.775 47.715 1.00 43.72 O ATOM 1416 O HOH G 51 9.009 49.996 33.051 1.00 51.94 O ATOM 1417 O HOH G 52 10.262 41.231 27.895 1.00 49.00 O ATOM 1418 O HOH G 53 13.720 13.669 12.813 0.33 18.06 O ATOM 1419 O HOH G 54 16.527 9.719 14.214 1.00 41.63 O ATOM 1420 O HOH G 55 19.917 −2.461 29.008 1.00 41.31 O ATOM 1421 O HOH G 56 26.002 4.113 27.927 1.00 43.02 O ATOM 1422 O HOH G 57 42.530 37.631 35.739 1.00 44.03 O ATOM 1423 O HOH G 58 0.558 23.097 29.764 1.00 38.42 O ATOM 1424 O HOH G 59 −0.084 20.766 28.679 1.00 42.63 O ATOM 1425 O HOH G 60 7.231 31.657 32.146 1.00 49.34 O ATOM 1426 O HOH G 61 6.100 28.757 33.751 1.00 48.45 O ATOM 1427 O HOH G 62 22.704 33.262 41.119 1.00 43.75 O ATOM 1428 O HOH G 63 23.542 36.678 45.283 1.00 56.29 O ATOM 1429 O HOH G 64 13.013 15.648 16.066 1.00 33.59 O ATOM 1430 O HOH G 65 11.923 11.539 37.896 1.00 32.51 O ATOM 1431 O HOH G 66 23.799 −0.422 30.808 1.00 42.75 O ATOM 1432 O HOH G 67 19.848 8.641 34.946 1.00 45.99 O ATOM 1433 O HOH G 68 6.284 8.088 36.246 1.00 32.45 O ATOM 1434 O HOH G 69 16.320 62.608 37.937 1.00 54.04 O ATOM 1435 O HOH G 70 17.347 60.408 34.261 1.00 51.34 O ATOM 1436 O HOH G 71 23.686 61.097 38.482 1.00 47.83 O ATOM 1437 O HOH G 72 1.261 5.929 31.480 1.00 26.59 O ATOM 1438 O HOH G 73 15.539 14.906 26.775 1.00 15.99 O ATOM 1439 O HOH G 74 14.984 14.225 17.521 1.00 25.28 O ATOM 1440 O HOH G 75 10.752 10.753 10.752 0.33 44.69 O ATOM 1441 O HOH G 76 7.951 0.926 3.374 1.00 52.97 O ATOM 1442 O HOH G 77 5.353 2.129 6.301 1.00 46.99 O ATOM 1443 O HOH G 78 3.761 3.646 2.822 0.33 23.22 O ATOM 1444 O HOH G 79 5.736 2.198 2.348 1.00 56.67 O ATOM 1445 O HOH G 80 16.996 15.731 17.621 1.00 32.02 O ATOM 1446 O HOH G 81 9.509 9.336 12.446 1.00 27.31 O ATOM 1447 O HOH G 82 7.285 63.628 41.255 1.00 50.12 O ATOM 1448 O HOH G 83 11.668 71.674 37.394 1.00 58.95 O ATOM 1449 O HOH G 84 52.502 27.817 39.209 1.00 54.21 O ATOM 1450 O HOH G 85 22.730 36.647 42.784 1.00 52.19 O ATOM 1451 O HOH G 86 17.005 45.986 32.923 1.00 30.94 O ATOM 1452 O HOH G 87 9.499 47.980 33.772 1.00 40.66 O ATOM 1453 O HOH G 88 5.052 56.415 38.430 1.00 55.24 O ATOM 1454 O HOH G 89 22.807 −1.144 25.460 1.00 42.51 O ATOM 1455 O HOH G 90 25.234 −1.919 25.883 1.00 52.43 O ATOM 1456 O HOH G 91 21.549 10.612 19.510 1.00 36.05 O ATOM 1457 O HOH G 92 8.615 −0.822 6.948 1.00 49.68 O ATOM 1458 O HOH G 93 11.375 −2.265 2.608 1.00 28.01 O ATOM 1459 O HOH G 94 10.563 −2.134 8.036 1.00 27.90 O ATOM 1460 O HOH G 95 3.858 −0.505 12.082 1.00 37.25 O ATOM 1461 O HOH G 96 17.845 62.184 36.568 1.00 60.67 O ATOM 1462 O HOH G 97 19.883 63.500 38.550 1.00 51.50 O ATOM 1463 O HOH G 98 −3.992 12.182 33.345 1.00 47.54 O ATOM 1464 O HOH G 99 −2.625 14.172 34.289 1.00 57.66 O ATOM 1465 O HOH H 1 −1.410 16.222 32.352 1.00 51.79 O ATOM 1466 O HOH H 2 −2.035 4.920 4.213 1.00 56.43 O ATOM 1467 O HOH H 3 1.762 2.181 3.138 0.33 9.55 O ATOM 1468 O HOH H 4 4.071 −1.142 2.376 1.00 70.24 O ATOM 1469 O HOH H 5 2.368 0.085 1.287 1.00 56.00 O ATOM 1470 O HOH H 6 3.459 −6.491 15.191 1.00 43.50 O ATOM 1471 O HOH H 7 2.611 −3.264 23.603 1.00 27.95 O ATOM 1472 O HOH H 8 2.170 0.591 19.746 1.00 52.43 O ATOM 1473 O HOH H 9 2.170 0.591 19.746 1.00 52.43 O ATOM 1474 O HOH H 10 22.207 28.317 48.743 1.00 45.79 O ATOM 1475 O HOH H 11 14.592 −1.036 24.606 1.00 38.07 O ATOM 1476 O HOH H 12 4.462 −4.943 21.408 1.00 41.79 O ATOM 1477 O HOH H 13 15.675 56.885 33.119 1.00 46.32 O ATOM 1478 O HOH H 14 18.469 51.763 36.153 1.00 38.33 O ATOM 1479 O HOH H 15 12.448 −6.521 8.382 1.00 45.62 O ATOM 1480 O HOH H 16 12.130 65.814 42.971 1.00 38.19 O ATOM 1481 O HOH H 17 25.958 29.229 39.247 1.00 44.50 O ATOM 1482 O HOH H 18 26.611 −2.745 16.970 1.00 51.78 O ATOM 1483 O HOH H 19 9.680 −2.081 21.897 1.00 38.19 O ATOM 1484 O HOH H 20 5.879 −4.835 25.822 1.00 40.98 O ATOM 1485 O HOH H 21 22.458 42.679 31.767 1.00 40.48 O ATOM 1486 O HOH H 22 12.241 −9.427 8.755 1.00 54.06 O ATOM 1487 O HOH H 23 5.205 −5.013 17.361 1.00 35.53 O ATOM 1488 O HOH H 24 16.473 −0.862 4.489 1.00 41.63 O ATOM 1489 O HOH H 25 7.860 61.368 30.803 1.00 53.11 O ATOM 1490 O HOH H 26 13.077 63.130 35.975 1.00 48.46 O ATOM 1491 O HOH H 27 42.305 36.490 37.769 1.00 45.84 O END 

1-44. (canceled)
 45. A method for selecting or designing a compound expected to modulate the activity of Leukotriene C4 synthase (LTC4S), the method comprising the step of using molecular modelling means to select or design a compound that is predicted to interact with the catalytic site or a substrate binding region of LTC4S, wherein a three-dimensional structure of at least a part of the catalytic site or a substrate binding region of LTC4S is compared with a three-dimensional structure of a compound, and a compound that is predicted to interact with the said catalytic site or substrate binding region is selected.
 46. The method of claim 45 wherein the three-dimensional structure of at least a part of the active site or a substrate binding region of LTC4S is a three-dimensional structure (or part thereof) determined for an LTC4S polypeptide comprising an N-terminal hexahistidine tag.
 47. The method of claim 45 wherein the three-dimensional structure of at least a part of the active site or a substrate binding region of LTC4S is a three-dimensional structure (or part thereof) determined for a human LTC4S polypeptide.
 48. The method of claim 45 wherein the three-dimensional structure of at least a part of the active site or a substrate binding region of LTC4S is a three-dimensional structure (or part thereof) obtainable by X-ray analysis of a crystal obtainable using a mother liquor solution comprising a detergent; and optionally, the mother liquor solution comprises glutathione (GSH).
 49. The method of claim 48 wherein the detergent is dodecyl maltoside (DDM).
 50. The method of claim 48 wherein the three-dimensional structure of at least a part of the active site or a substrate binding region of LTC4S is that represented by the structure co-ordinates shown in Table I (or a part thereof) when the mother liquor solution does not comprise GSH, or Table II (or a part thereof) when the mother liquor solution comprises GSH; or a structure modelled on such structure co-ordinates ± the root mean square deviation from the backbone atoms of the protein of less than 2.0 Å, 1.5, Å 1.0 Å or 0.5 Å.
 51. The method of claim 45 wherein the selected compound is predicted to block or bind to at least a part of a region of the structure termed the “GSH substrate binding cavity” (formed by residues including residues Arg51, Arg30, Arg104, Gln53, Asn55, Glu58, Tyr59, Tyr93, Tyr97, Ile27, Pro37, Leu108 of full length human LTC4S, or equivalent residues); the “lipophilic substrate binding crevice” (formed by residues including Ala20, Leu24, Ile27, Tyr59, Trp116, Ala112, Leu115, Leu108, Tyr109, Leu62, Val119, Thr66, Val16 and Leu17, or equivalent residues); or the “catalytic site” (formed by residues including Arg104 or Arg31, or equivalent residues).
 52. The method of claim 45 comprising the step of assessing whether the compound modulates the activity of LTC4S, and selecting a compound that modulates the activity.
 53. The method of claim 45 comprising the step of assessing whether the compound modulates LTC4 signalling in a whole cell, tissue or organism, and a compound that modulates the activity is selected; and, optionally further comprising the step of assessing whether the compound modulates the activity of LTC4S in the whole cell, tissue or organism, and a compound that modulates the activity is selected.
 54. A three-dimensional crystalline form of LTC4S as defined in claim 45 belonging to space group F23 and/or has a unit cell containing 48 LTC4S chains and/or comprises multiple adjacent histidine tags coordinated by metal ions (for example three for each LTC4S trimer or twelve for each unit cell).
 55. The three-dimensional crystalline form of claim 54 wherein the crystalline form further comprises a co-crystallised molecule; and, optionally, the co-crystallised molecule modulates LTC4S activity.
 56. The three-dimensional crystalline form of claim 55 wherein the co-crystallised molecule is GSH or a detergent such as DDM.
 57. Use of LTC4S as defined in claim 45 in generating a structure of the active site or a substrate binding region (or part thereof) of LTC4S; or a structure of the active site or a substrate binding region (or part thereof) of LTC4S bound to a test compound.
 58. A method of predicting a three dimensional structure of a target LTC4S protein or other MAPEG family member protein or homo- or heteromultimer thereof (the target protein), the method comprises the steps of: aligning a representation of an amino acid sequence of the target protein with the amino acid sequence of the LTC4S of Table I or II, optionally varied by a root mean square deviation of not more than 2.0 Å, 1.5 Å, 1.0 Å or 0.5 Å, or selected coordinates thereof, to match homologous regions of the amino acid sequences; modelling the structure of the matched homologous regions of said target protein on the corresponding regions of the LTC4S structure as defined by Table I or II, optionally varied by a root mean square deviation of not more than 2.0 Å, 1.5 Å, 1.0 Å or 0.5 Å, or selected coordinates thereof; and determining a conformation for said target protein which substantially preserves the structure of said matched homologous regions.
 59. A method for selecting or designing a compound expected to modulate the activity of a MAPEG family member protein or homo- or heteromultimer thereof, the method comprising the step of using molecular modelling means to select or design a compound that is predicted to interact with the catalytic site or a substrate binding region of the MAPEG family member protein or homo- or heteromultimer thereof, wherein a three-dimensional structure of at least a part of the catalytic site or a substrate binding region of the MAPEG family member protein or homo- or heteromultimer thereof is compared with a three-dimensional structure of a compound, and a compound that is predicted to interact with the said catalytic site or substrate binding region is selected, wherein the three-dimensional structure of at least a part of the catalytic site or a substrate binding region of the MAPEG protein or homo- or heteromultimer thereof is a three-dimensional structure (or part thereof) predicted by a method according to claim
 58. 60. The method of claim 45 wherein the molecular structure to be fitted is in the form of a model of a pharmacophore.
 61. A computer-based method of rational drug design comprising: (a) providing the coordinates of a LTC4S structure as defined in Table I or II optionally varied by a root mean square deviation of backbone atoms of the protein of less than 2.0 Å, 1.5 Å, 1.0 Å or 0.5 Å, or selected coordinates thereof; (b) providing the structures of a plurality of molecular fragments; (c) fitting the structure of each of the molecular fragments to the selected coordinates; and (d) assembling the molecular fragments into a single molecule to form a candidate modulator molecule; and, optionally further comprising the step of: (e) obtaining or synthesising the molecular fragment or modulator molecule; and (f) contacting the molecular fragment or modulator molecule with LTC4S to determine the ability of the molecular fragment or modulator molecule to interact with LTC4S.
 62. A method of obtaining a representation of the three dimensional structure of LTC4S, which method comprises providing the data of Table I or II optionally varied by a root mean square deviation of backbone atoms of the protein of less than 2.0 Å, 1.5 Å, 1.0 Å or 0.5 Å, or selected coordinates thereof, and constructing a three-dimensional structure representing said coordinates; and, optionally presenting the structure as a (a) a wire-frame model; (b) a chicken-wire model; (c) a ball-and-stick model; (d) a space-filling model; (e) a stick-model; (f) a ribbon model; (g) a snake model; (h) an arrow and cylinder model; (i) an electron density map; (j) a molecular surface model.
 63. A computer system, intended to generate structures and/or perform optimisation of compounds which interact with LTC4S or other MAPEG family member protein or homo- or heteromultimer thereof, complexes of LTC4S or other MAPEG family member protein or homo- or heteromultimer thereof with compounds, the system containing computer-readable data comprising one or more of: (a) LTC4S co-ordinate data of Tables I or II optionally varied by a root mean square deviation of backbone atoms of the protein of less than 22.0 Å, 1.5 Å, 1.0 Å or 0.5 Å, or selected coordinates thereof, said data defining the three-dimensional structure of LTC4S or said selected coordinates thereof; (b) atomic coordinate data of a target MAPEG family member protein or homo- or heteromultimer thereof generated by homology modelling of the target based on the coordinate data of Table I or II optionally varied by a root mean square deviation of backbone atoms of the protein of less than 2.0 Å, 1.5 Å, 1.0 Å or 0.5 Å, or selected coordinates thereof; (c) atomic coordinate data of a target MAPEG family member protein or homo- or heteromultimer thereof generated by interpreting X-ray crystallographic data or NMR data by reference to the coordinate data of Tables I or II optionally varied by a root mean square deviation of backbone atoms of the protein of less than 2.0 Å, 1.5 Å, 1.0 Å or 0.5 Å, or selected coordinates thereof; (d) structure factor data derivable from the atomic coordinate data of (b) or (c); and (e) atomic coordinate data of Table I or II optionally varied by a root mean square deviation of backbone atoms of the protein of less than 2.0 Å, 1.5 Å, 1.0 Å or 0.5 Å, or selected coordinates thereof, wherein, optionally, the atomic coordinate data is for at least one of the atoms provided by the residues listed in claim
 51. 64. A method for selecting or designing a compound expected to modulate the activity of Leukotriene C4 synthase (LTC4S), the method comprising the step of using molecular modelling means to select or design a compound that is predicted to interact with a subunit interaction region of LTC4S, wherein a three-dimensional structure of at least a part of a subunit interaction region of LTC4S is compared with a three-dimensional structure of a compound, and a compound that is predicted to interact with the said substrate interaction region is selected. 